KASH5
protein-codingKASH domain containing 5, the group of KASH domain containing
Gene summary
Predicted to enable dynein complex binding activity. Predicted to be involved in several processes, including cytoskeleton organization; homologous chromosome segregation; and spindle localization. Predicted to act upstream of or within several processes, including double-strand break repair via homologous recombination; meiotic telomere clustering; and spermatogenesis. Predicted to be located in nuclear envelope. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in chromosome; meiotic spindle pole; and nuclear outer membrane. Implicated in primary ovarian insufficiency and spermatogenic failure 88. [provided by Alliance of Genome Resources, Jun 2026]
- CCDC155
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Genitourinary; Obstetric
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KASH5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144688.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 1 | 1 | 89 | 9 | 100 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 4 | 2 | 89 | 11 | 0 | 106 |
Highest pathogenic variant AF is 0.0013597922
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_653289.3 | 19 | MANE Select | |
| Ensembl | ENSP00000404220.2 | 19 | MANE Select | |
| Ensembl | ENSP00000469435.1 | 6 | Standard | |
| Ensembl | ENSP00000468838.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- double-strand break repair via homologous recombination
- actin filament organization
- synapsis
- spermatogenesis
- telomere localization
Molecular Function
- protein binding
- identical protein binding
- dynein complex binding
Cellular Component
- chromosome, telomeric region
- lateral element
- nuclear outer membrane
- integral component of membrane
- meiotic nuclear membrane microtubule tethering complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000447857
- Coding exons
- 19
- Length
- 29777
- Individuals with no LoFs
- 124596
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 62
- Defined
- 124658
- p
- 0.000249
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.17 | 253 | 311 | 0.813 | 0.0000179 | 3524 |
| Missense (PolyPhen) | 40 | 67.413 | 0.59335 | 943 | ||
| Synonymous | 2.03 | 95 | 124 | 0.768 | 0.00000656 | 1141 |
| Loss of Function | 2.54 | 20 | 36.6 | 0.546 | 0.00000175 | 408 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00027 | 0.00026 | rare |
| Latino/Admixed American | 0.00045 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00023 | 0.00023 | rare |
| South Asian | 0.00039 | 0.00036 | rare |
| Other | 0.00086 | 0.00083 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Required for telomere attachment to nuclear envelope in the prophase of meiosis and for rapid telomere prophase movements implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly. Required for homologue pairing during meiotic prophase in spermatocytes and probably oocytes. Essential for male and female gametogenesis. Recruits cytoplasmic dynein to telomere attachment sites at the nuclear envelope in spermatocytes. In oocytes is involved in meiotic resumption and spindle formation. {ECO:0000250|UniProtKB:Q80VJ8}.;
Recessive Scores
- pRec
- 0.0788
Intolerance Scores
- LoFtool
- 0.914
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.242
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |