KATNAL1

Chr 13

katanin catalytic subunit A1 like 1

NCBI Gene: 84056ENSG00000102781UniProt: Q9BW62

The protein is an ATP-dependent microtubule-severing enzyme that regulates microtubule dynamics, particularly in Sertoli cells where it is essential for spermiogenesis and male fertility. Mutations cause autosomal recessive male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF), resulting in asthenozoospermia and oligozoospermia. The gene is highly constrained against loss-of-function variants, indicating its critical cellular role.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
35
P/LP submissions
0%
P/LP missense
0.44
LOEUF
DN
Mechanism· predicted
Clinical Summary— KATNAL1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 56 VUS of 115 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.532
Z-score 3.59
OE 0.21 (0.11–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.60Z-score
OE missense 0.72 (0.64–0.81)
190 obs / 263.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.11–0.44)
0≤0.351.4
Missense OE0.72 (0.64–0.81)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 5 / 23.9Missense obs/exp: 190 / 263.2Syn Z: 0.55
DN
0.6743th %ile
GOF
0.5660th %ile
LOF
0.4135th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic2
VUS56
Likely Benign2
33
Pathogenic
2
Likely Pathogenic
56
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
2
0
2
VUS
0
52
4
0
56
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total05439093

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KATNAL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients