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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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CPAMD8
C3 and PZP like alpha-2-macroglobulin domain containing 8
Chromosome 19 Β· 19p13.11
NCBI Gene: 27151Ensembl: ENSG00000160111HGNC: HGNC:23228UniProt: A0A494C0S9
19PubMed Papers
21Diseases
0Drugs
27Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
eye developmentendopeptidase inhibitor activityextracellular regionGO:0005615Familial ocular anterior segment mesenchymal dysgenesisanterior segment dysgenesiscataractOcular anterior segment dysgenesis
✦AI Summary

CPAMD8 is a member of the complement 3/alpha-2-macroglobulin protein family with primary roles in eye development and innate immunity 1. The gene encodes a 1885-amino acid protein containing a signal sequence, thioester motif, and unique Kazal-type serine proteinase inhibitor domain at its C-terminus 1. CPAMD8 is highly expressed in neural crest-derived tissues of the anterior eye segment, particularly in the nonpigmented epithelium of the iris and ciliary body, as well as in the optic nerve and retina 23. Functionally, CPAMD8 likely participates in ocular anterior segment formation and may regulate drainage structures critical for intraocular pressure homeostasis 3. Biallelic CPAMD8 variants cause autosomal recessive anterior segment dysgenesis and primary congenital glaucoma 45. Additionally, biallelic variants are significantly associated with childhood and juvenile open-angle glaucoma, pigmentary glaucoma, and primary angle-closure glaucoma, representing the second most common inherited cause of childhood glaucoma after CYP1B1 326. Affected individuals frequently present with iris abnormalities, cataracts, and retinal detachment, with most requiring surgical intervention to control elevated intraocular pressure 3.

Sources cited
1
CPAMD8 is a complement 3/alpha-2-macroglobulin family member with 1885 amino acids, containing thioester motif and C-terminal Kazal domain; expressed in kidney, brain, and testis
PMID: 15177561
2
Biallelic CPAMD8 variants enriched in glaucoma patients; protein localized to nonpigmented iris epithelium and ciliary process; mRNA highly expressed in optic nerve, ciliary body, retina, and iris
PMID: 34154991
3
Biallelic CPAMD8 variants cause 5.7% of childhood glaucoma and 2.1% of juvenile open-angle glaucoma; highest expression in neural crest-derived anterior segment tissues; associated with iris abnormalities (81.8%), cataracts (72.7%), and retinal detachment (27.3%)
PMID: 32085876
4
CPAMD8 strikingly expressed in human fetal lens and distal neural retina; mutations linked to anterior segment dysgenesis and primary congenital glaucoma
PMID: 39978205
5
CPAMD8 is A2M/C3 family protein predominantly expressed in distal retinal neuroepithelium forming iris and ciliary body; mutations linked to anterior segment dysplasia and congenital glaucoma
PMID: 39603092
6
Compound heterozygous CPAMD8 variants associated with pigmentary glaucoma in autosomal recessive inheritance pattern; identified in 11 of 38 sporadic pigmentary glaucoma patients
PMID: 35957697
7
CPAMD8 variants implicated in anterior segment dysgenesis and iris abnormalities; listed among genetic causes to consider in differential diagnosis of congenital aniridia
PMID: 40138169
Disease Associationsβ“˜21
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.72Strong
anterior segment dysgenesisOpen Targets
0.53Moderate
cataractOpen Targets
0.46Moderate
Ocular anterior segment dysgenesisOpen Targets
0.40Weak
glaucomaOpen Targets
0.37Weak
retinal detachmentOpen Targets
0.37Weak
lens diseaseOpen Targets
0.35Weak
congenital glaucomaOpen Targets
0.34Weak
Juvenile glaucomaOpen Targets
0.34Weak
eye diseaseOpen Targets
0.29Weak
major salivary gland cancerOpen Targets
0.28Weak
tooth diseaseOpen Targets
0.28Weak
Abnormal anterior eye segment morphologyOpen Targets
0.27Weak
gastrointestinal diseaseOpen Targets
0.26Weak
pleural empyemaOpen Targets
0.23Weak
pneumothoraxOpen Targets
0.23Weak
gram-negative bacterial infectionsOpen Targets
0.23Weak
genetic disorderOpen Targets
0.19Weak
breast ductal adenocarcinomaOpen Targets
0.11Weak
Abnormality of the skeletal systemOpen Targets
0.04Suggestive
Anterior segment dysgenesis 8UniProt
Pathogenic Variants27
NM_015692.5(CPAMD8):c.2211dup (p.Arg738fs)Pathogenic
Anterior segment dysgenesis 8|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 738
NM_015692.5(CPAMD8):c.1881del (p.Arg627fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 627
NM_015692.5(CPAMD8):c.3349C>T (p.Arg1117Ter)Likely pathogenic
Anterior segment dysgenesis 8|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1117
NM_015692.5(CPAMD8):c.1758+1_1758+4delPathogenic
Anterior segment dysgenesis 8|not provided
β˜…β˜…β˜†β˜†2024
NM_015692.5(CPAMD8):c.2070+1G>APathogenic
not provided|Familial cancer of breast|Anterior segment dysgenesis 8
β˜…β˜…β˜†β˜†2024
NM_015692.5(CPAMD8):c.4157C>A (p.Thr1386Asn)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 1386
NM_015692.5(CPAMD8):c.2270del (p.Asn757fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 757
NM_015692.5(CPAMD8):c.1689C>A (p.Tyr563Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 563
NM_015692.5(CPAMD8):c.2070_2071insTTAA (p.Glu691fs)Likely pathogenic
Anterior segment dysgenesis 8
β˜…β˜†β˜†β˜†2025β†’ Residue 691
NM_015692.5(CPAMD8):c.404A>T (p.Asp135Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 135
NM_015692.5(CPAMD8):c.3145-1G>TLikely pathogenic
Anterior segment dysgenesis 8
β˜…β˜†β˜†β˜†2024
NM_015692.5(CPAMD8):c.4396del (p.Gln1466fs)Likely pathogenic
Anterior segment dysgenesis 8
β˜…β˜†β˜†β˜†2024β†’ Residue 1466
NM_015692.5(CPAMD8):c.534G>A (p.Trp178Ter)Likely pathogenic
Anterior segment dysgenesis 8
β˜…β˜†β˜†β˜†2024β†’ Residue 178
NM_015692.5(CPAMD8):c.4825C>T (p.Arg1609Ter)Likely pathogenic
Anterior segment dysgenesis 8
β˜…β˜†β˜†β˜†2024β†’ Residue 1609
NM_015692.5(CPAMD8):c.4407+2T>GLikely pathogenic
CPAMD8-related disorder
β˜…β˜†β˜†β˜†2023
NM_015692.5(CPAMD8):c.3724del (p.Gln1242fs)Likely pathogenic
CPAMD8-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 1242
NM_015692.5(CPAMD8):c.3798_3861+1759delPathogenic
Glaucoma 3A
β˜…β˜†β˜†β˜†2023
NM_015692.5(CPAMD8):c.1691dup (p.Arg565fs)Likely pathogenic
Abnormal anterior eye segment morphology
β˜…β˜†β˜†β˜†2022β†’ Residue 565
NM_015692.5(CPAMD8):c.2002C>T (p.Arg668Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 668
NM_015692.5(CPAMD8):c.114_117del (p.Ser39fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 39
View on ClinVar β†—
Related Genes
MAB21L1Shared pathway50%SALL2Shared pathway50%MAB21L2Shared pathway50%PMELShared pathway33%SIX6Shared pathway33%ABCB5Shared pathway33%
Tissue Expression6 tissues
Lung
100%
Heart
63%
Ovary
35%
Brain
25%
Liver
6%
Bone Marrow
5%
Gene Interaction Network
Click a node to explore
CPAMD8MAB21L1SALL2MAB21L2PMELSIX6ABCB5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8IZJ3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.82LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.71 [0.62–0.82]
RankingsWhere CPAMD8 stands among ~20K protein-coding genes
  • #14,390of 20,598
    Most Researched19
  • #1,924of 5,498
    Most Pathogenic Variants27
  • #7,017of 17,882
    Most Constrained (LOEUF)0.82
Genes detectedCPAMD8
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
CPAMD8, a New Gene for Anterior Segment Dysgenesis and Childhood Glaucoma.
PMID: 32444017
Ophthalmology Β· 2020
1.00
2
Biallelic variants in
PMID: 34154991
Br J Ophthalmol Β· 2022
0.90
3
Generation of a homozygous CPAMD8 knockout human embryonic stem cell line (WAe009-A-2R) by CRISPR/Cas9 system.
PMID: 39978205
Stem Cell Res Β· 2025
0.80
4
Establishment of a CPAMD8-GFP reporter human embryonic stem cell line, IBBDe001-B, using CRISPR/Cas9 editing.
PMID: 39603092
Stem Cell Res Β· 2024
0.70
5
Biallelic CPAMD8 Variants Are a Frequent Cause of Childhood and Juvenile Open-Angle Glaucoma.
PMID: 32085876
Ophthalmology Β· 2020
0.60