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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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QRICH2
glutamine rich 2
Chromosome 17 Β· 17q25.1
NCBI Gene: 84074Ensembl: ENSG00000129646.16HGNC: HGNC:25326UniProt: A0A1B0GW36
11PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcell projection assemblyflagellated sperm motilitynegative regulation of ubiquitin-dependent protein catabolic processazoospermiagoutspermatogenic failure 7spermatogenic failure 79
✦AI Summary

QRICH2 encodes a glutamine-rich protein essential for sperm flagella biogenesis and male fertility. Mechanistically, QRICH2 stabilizes proteins involved in flagellar development and acts as a suppressor of ubiquitin-dependent protein degradation 1. Recent evidence reveals QRICH2 functions as a glutamine sensor regulating microtubule glutamylation, which is critical for flagellar structural integrity and sperm motility 2. Additionally, QRICH2 possesses profound antioxidant properties that protect spermatids from reactive oxygen species (ROS)-induced DNA damage, autophagy, and apoptosis, thereby promoting spermatozoa survival 3. QRICH2 interacts with AKAP4 in the sperm fibrous sheath, and disruption of this interaction impairs flagellar development 4. Loss-of-function mutations in QRICH2 cause multiple morphological abnormalities of the sperm flagella (MMAF) and nonobstructive azoospermia, with homozygous variants identified in infertile males 15. Heterozygous QRICH2 variants are associated with asthenozoospermia and sperm tail defects 6. Whole-genome sequencing studies identify QRICH2 among candidate genes for nonobstructive azoospermia 7. QRICH2 represents a critical genetic target for understanding idiopathic male infertility pathogenesis.

Sources cited
1
Loss-of-function QRICH2 mutations cause MMAF and male infertility; QRICH2 stabilizes proteins related to flagellar development
PMID: 30683861
2
QRICH2 functions as a glutamine sensor regulating microtubule glutamylation and mitochondrial function in sperm flagella
PMID: 38597976
3
QRICH2 possesses antioxidant capacity protecting spermatids from ROS-induced damage and promoting spermatozoa viability
PMID: 38772286
4
QRICH2 interacts with AKAP4; reduced AKAP4 expression decreases QRICH2 expression and causes dysplastic fibrous sheath
PMID: 34415320
5
Homozygous loss-of-function QRICH2 mutations confirmed in MMAF patients; heterozygous variants not significantly associated with MMAF
PMID: 31292949
6
Heterozygous QRICH2 variants associated with asthenozoospermia and sperm tail-specific abnormalities
PMID: 40107860
7
QRICH2 identified as candidate gene for nonobstructive azoospermia via whole-genome sequencing
PMID: 36017582
Disease Associationsβ“˜21
azoospermiaOpen Targets
0.71Strong
goutOpen Targets
0.39Weak
spermatogenic failure 7Open Targets
0.08Suggestive
spermatogenic failure 79Open Targets
0.08Suggestive
spermatogenic failure 58Open Targets
0.08Suggestive
spermatogenic failure 10Open Targets
0.08Suggestive
spermatogenic failure 11Open Targets
0.08Suggestive
spermatogenic failure 65Open Targets
0.08Suggestive
spermatogenic failure 84Open Targets
0.08Suggestive
spermatogenic failure 93Open Targets
0.08Suggestive
spermatogenic failure 56Open Targets
0.08Suggestive
spermatogenic failure 92Open Targets
0.08Suggestive
spermatogenic failure 94Open Targets
0.08Suggestive
spermatogenic failure 47Open Targets
0.08Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.08Suggestive
spermatogenic failure 40Open Targets
0.08Suggestive
spermatogenic failure 76Open Targets
0.08Suggestive
spermatogenic failure 80Open Targets
0.08Suggestive
spermatogenic failure 54Open Targets
0.08Suggestive
spermatogenic failure 64Open Targets
0.08Suggestive
Spermatogenic failure 35UniProt
Pathogenic Variants10
NM_001388453.1(QRICH2):c.1507C>T (p.Gln503Ter)Likely pathogenic
Spermatogenic failure 35
β˜…β˜†β˜†β˜†2023β†’ Residue 503
NM_001388453.1(QRICH2):c.3952_3953del (p.Arg1318fs)Likely pathogenic
Spermatogenic failure 35
β˜…β˜†β˜†β˜†2023β†’ Residue 1318
NM_001388453.1(QRICH2):c.4914dup (p.Asn1639fs)Likely pathogenic
QRICH2-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 1639
NM_001388453.1(QRICH2):c.5171dup (p.Ser1725fs)Likely pathogenic
Spermatogenic failure 35
β˜…β˜†β˜†β˜†2022β†’ Residue 1725
NM_001388453.1(QRICH2):c.5266-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2021
NM_001388453.1(QRICH2):c.690G>A (p.Trp230Ter)Pathogenic
Spermatogenic failure 35
β˜†β˜†β˜†β˜†2025β†’ Residue 230
NM_001388453.1(QRICH2):c.3535C>T (p.Arg1179Ter)Pathogenic
Spermatogenic failure 35
β˜†β˜†β˜†β˜†2025β†’ Residue 1179
NM_001388453.1(QRICH2):c.5482+1G>ALikely pathogenic
QRICH2-related disorder
β˜†β˜†β˜†β˜†2024
NM_001388453.1(QRICH2):c.5112C>G (p.Tyr1704Ter)Pathogenic
Spermatogenic failure 35
β˜†β˜†β˜†β˜†2020β†’ Residue 1704
NM_001388453.1(QRICH2):c.3999C>G (p.Tyr1333Ter)Pathogenic
Spermatogenic failure 35
β˜†β˜†β˜†β˜†2020β†’ Residue 1333
View on ClinVar β†—
Related Genes
CFAP44Protein interaction81%CFAP43Protein interaction79%QRICH1Protein interaction74%CFAP69Protein interaction71%DNAH1Protein interaction70%DMWDShared pathway33%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
40%
Ovary
23%
Lung
22%
Heart
11%
Brain
7%
Gene Interaction Network
Click a node to explore
QRICH2CFAP44CFAP43QRICH1CFAP69DNAH1DMWD
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9H0J4
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.83LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.71 [0.61–0.83]
RankingsWhere QRICH2 stands among ~20K protein-coding genes
  • #16,875of 20,598
    Most Researched11
  • #2,900of 5,498
    Most Pathogenic Variants10
  • #7,117of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedQRICH2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.
PMID: 30683861
Nat Commun Β· 2019
1.00
2
Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia.
PMID: 36017582
Andrology Β· 2022
0.90
3
Genetic variants in
PMID: 40107860
Libyan J Med Β· 2025
0.80
4
Cerebrospinal Fluid Protein Biomarker Discovery in CLN3.
PMID: 37338096
J Proteome Res Β· 2023
0.70
5
A Key regulatory protein QRICH2 governing sperm function with profound antioxidant properties, enhancing sperm viability.
PMID: 38772286
Reprod Biol Β· 2024
0.60