HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KASH5
KASH domain containing 5
Chromosome 19 Β· 19q13.33
NCBI Gene: 147872Ensembl: ENSG00000161609.10HGNC: HGNC:26520UniProt: Q8N6L0
25PubMed Papers
22Diseases
0Drugs
7Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingdynein complex bindingactin filament organizationhomologous chromosome pairing at meiosisspermatogenic failure 88premature ovarian failure 22azoospermiagenetic non-acquired premature ovarian failure
✦AI Summary

KASH5 is a meiosis-specific component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex that plays a critical role in gametogenesis 1. The protein localizes exclusively at telomeres during prophase I of meiosis in both spermatocytes and oocytes, where it forms a complex with SUN1 to connect telomeres to the nuclear envelope 1. This KASH5-SUN1 complex is essential for homologous chromosome 19 and meiotic chromosome 19 by recruiting cytoplasmic dynein to telomere attachment sites 1. Pathogenic variants in KASH5 cause severe reproductive disorders including premature ovarian insufficiency (POI) and non-obstructive azoospermia 23. These mutations disrupt KASH5 localization and its interaction with SUN1, leading to defective meiotic homolog pairing and accelerated oocyte depletion 2. Clinical studies have identified KASH5 variants in patients with POI, recurrent miscarriage, and male infertility, demonstrating sexual dimorphism in phenotype severity 45. The protein's transmembrane domain is critical for proper localization, as certain variants cause mistargeting to mitochondria rather than the nuclear envelope 6.

Sources cited
1
KASH5 is a meiosis-specific KASH domain protein that localizes at telomeres and interacts with SUN1 and dynein complex
PMID: 22826121
2
KASH5 variants cause premature ovarian insufficiency through defective meiotic homolog pairing
PMID: 35708642
3
KASH5 variants are associated with non-obstructive azoospermia and meiotic arrest
PMID: 35674372
4
KASH5 mutations show sexual dimorphism in reproductive phenotypes
PMID: 36864840
5
KASH5 is identified as a POI-associated gene with higher burden of loss-of-function variants
PMID: 36732629
6
KASH5 transmembrane domain variants cause protein mislocalization to mitochondria
PMID: 33980926
Disease Associationsβ“˜22
spermatogenic failure 88Open Targets
0.50Moderate
premature ovarian failure 22Open Targets
0.45Moderate
azoospermiaOpen Targets
0.35Weak
genetic non-acquired premature ovarian failureOpen Targets
0.27Weak
partial chromosome Y deletionOpen Targets
0.06Suggestive
primary ovarian insufficiencyOpen Targets
0.06Suggestive
spinocerebellar ataxia type 32Open Targets
0.05Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.05Suggestive
isochromosomy YpOpen Targets
0.05Suggestive
Isolated follicle stimulating hormone deficiencyOpen Targets
0.05Suggestive
spermatogenic failure 57Open Targets
0.05Suggestive
spermatogenic failure 50Open Targets
0.05Suggestive
partial androgen insensitivity syndromeOpen Targets
0.05Suggestive
spermatogenic failure 25Open Targets
0.05Suggestive
spermatogenic failure 71Open Targets
0.05Suggestive
spermatogenic failure 63Open Targets
0.05Suggestive
ring chromosome YOpen Targets
0.05Suggestive
isochromosomy YqOpen Targets
0.05Suggestive
46,XX gonadal dysgenesisOpen Targets
0.05Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.05Suggestive
Premature ovarian failure 22UniProt
Spermatogenic failure 88UniProt
Pathogenic Variants7
NM_144688.5(KASH5):c.747G>A (p.Ala249=)Likely pathogenic
Genetic non-acquired premature ovarian failure|Premature ovarian failure 22|Hepatocellular carcinoma
β˜…β˜†β˜†β˜†2021β†’ Residue 249
NM_144688.5(KASH5):c.590T>C (p.Leu197Pro)Pathogenic
Spermatogenic failure 88|Premature ovarian failure 22
β˜†β˜†β˜†β˜†2023β†’ Residue 197
NM_144688.5(KASH5):c.981_982del (p.Arg327fs)Pathogenic
Spermatogenic failure 88
β˜†β˜†β˜†β˜†2023β†’ Residue 327
NM_144688.5(KASH5):c.-95-2_798+248delPathogenic
Spermatogenic failure 88
β˜†β˜†β˜†β˜†2023
NM_144688.5(KASH5):c.1271_1274del (p.Arg424fs)Pathogenic
Premature ovarian failure 22|Spermatogenic failure 88
β˜†β˜†β˜†β˜†2023β†’ Residue 424
NM_144688.5(KASH5):c.1604T>A (p.Leu535Gln)Pathogenic
Spermatogenic failure 88
β˜†β˜†β˜†β˜†2023β†’ Residue 535
NM_144688.5(KASH5):c.1146+5G>APathogenic
Azoospermia
β˜†β˜†β˜†β˜†2021
View on ClinVar β†—
Related Genes
SUN2Protein interaction99%SYNE1Protein interaction92%SYNE3Protein interaction91%SYNE2Protein interaction84%SUN1Protein interaction82%SUN5Protein interaction78%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
50%
Liver
35%
Brain
10%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
KASH5SUN2SYNE1SYNE3SYNE2SUN1SUN5
PROTEIN STRUCTURE
Preparing viewer…
PDB6R2I Β· 1.54 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.09LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.89 [0.74–1.09]
RankingsWhere KASH5 stands among ~20K protein-coding genes
  • #13,003of 20,598
    Most Researched25
  • #3,260of 5,498
    Most Pathogenic Variants7
  • #11,133of 17,882
    Most Constrained (LOEUF)1.09
Genes detectedKASH5
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Landscape of pathogenic mutations in premature ovarian insufficiency.
PMID: 36732629
Nat Med Β· 2023
1.00
2
Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles.
PMID: 39545410
J Clin Invest Β· 2024
0.90
3
A human infertility-associated KASH5 variant promotes mitochondrial localization.
PMID: 33980926
Sci Rep Β· 2021
0.80
4
Homozygous Variant in KASH5 Causes Premature Ovarian Insufficiency by Disordered Meiotic Homologous Pairing.
PMID: 35708642
J Clin Endocrinol Metab Β· 2022
0.70
5
Novel bi-allelic variants in KASH5 are associated with meiotic arrest and non-obstructive azoospermia.
PMID: 35674372
Mol Hum Reprod Β· 2022
0.60