KRTAP10-11

Chr 21

keratin associated protein 10-11

Also known as: KAP10.11, KAP18.11, KRTAP18-11, KRTAP18.11

NCBI Gene: 386678 ENSG00000243489 UniProt: P60412

This gene encodes a hair keratin-associated protein that forms disulfide cross-links with hair keratins to create the rigid structure of the hair shaft through extensive cysteine residue interactions. The gene shows low constraint to loss-of-function variation (pLI = 0.0004, LOEUF = 1.4), suggesting mutations are likely to be tolerated. No established Mendelian disease associations have been reported for this gene.

Summary from RefSeq, UniProt

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Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.40

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— KRTAP10-11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

88 unique Pathogenic / Likely Pathogenic· 85 VUS of 197 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.40LOEUF

pLI 0.000

Z-score 0.76

OE 0.72 (0.39–1.40)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-1.60Z-score

OE missense 1.35 (1.21–1.51)

224 obs / 166.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE0.72 (0.39–1.40)

0≤0.351.4

Missense OE1.35 (1.21–1.51)

0≤0.61.4

Synonymous OE1.36

0≤1.21.6

LoF obs/exp: 6 / 8.4Missense obs/exp: 224 / 166.0Syn Z: -2.48

0.90top 5%

GOF

0.82top 10%

LOF

0.3163th %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.