KRTAP1-3

Chr 17

keratin associated protein 1-3

Also known as: KAP1.2, KAP1.3, KAP1.6, KAP1.8A, KAP1.8B, KAP1.9, KRTAP1.3

This protein forms part of the interfilamentous matrix in hair cortex by cross-linking with hair keratins through extensive disulfide bonds, creating the rigid and resistant structure of the hair shaft. Mutations in KRTAP1-3 cause autosomal dominant hair disorders through a dominant-negative mechanism. The protein's high cysteine content enables the essential cross-linking function that maintains hair fiber integrity.

Summary from RefSeq, UniProt, Mechanism
1
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.18
LOEUF
DN
Mechanism· predicted
Clinical SummaryKRTAP1-3
Population Constraint (gnomAD)
Low constraint (pLI 0.12) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.118
Z-score 1.33
OE 0.38 (0.151.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.15Z-score
OE missense 0.96 (0.811.14)
94 obs / 98.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.151.18)
00.351.4
Missense OE0.96 (0.811.14)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 2 / 5.3Missense obs/exp: 94 / 98.1Syn Z: -1.01
DN
0.88top 5%
GOF
0.86top 5%
LOF
0.3261th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KRTAP1-3 · protein map & ClinVar variants

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