KRTAP9-9

Chr 17

keratin associated protein 9-9

Also known as: KAP9.5, KAP9.9, KRTAP9-5, KRTAP9.9

NCBI Gene: 81870ENSG00000198083UniProt: Q9BYP9

This protein forms a matrix with keratin intermediate filaments through extensive disulfide bond cross-linking, creating the rigid and resistant structure of hair shafts. Mutations in KRTAP9-9 are predicted to cause disease through a dominant-negative mechanism. The gene shows tolerance to loss-of-function variants (pLI 0.29, LOEUF 1.89), but specific associated diseases have not been established.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
0
Pubs (1 yr)
7
P/LP submissions
0%
P/LP missense
1.89
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— KRTAP9-9
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 26 VUS of 37 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.290
Z-score 0.27
OE 0.00 (0.00–1.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.02Z-score
OE missense 1.30 (1.12–1.52)
117 obs / 89.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–1.89)
0≤0.351.4
Missense OE1.30 (1.12–1.52)
0≤0.61.4
Synonymous OE1.66
0≤1.21.6
LoF obs/exp: 0 / 0.1Missense obs/exp: 117 / 89.9Syn Z: -3.07
DN
0.91top 5%
GOF
0.86top 5%
LOF
0.3550th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

37 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
VUS26
Likely Benign4
7
Pathogenic
26
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
25
1
0
26
Likely Benign
0
2
2
0
4
Benign
0
0
0
0
0
Total02710037

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

View in ClinVar →

Protein Context — Lollipop Plot

KRTAP9-9 · 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 →

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