KRTAP10-4

Chr 21

keratin associated protein 10-4

Also known as: KAP10.4, KAP18-4, KRTAP10.4, KRTAP18-4, KRTAP18.4

NCBI Gene: 386672 ENSG00000215454 UniProt: P60372

The encoded keratin-associated protein forms disulfide bonds with hair keratins to create the rigid structural matrix of hair shafts. Mutations in this gene are associated with autosomal recessive woolly hair, a condition characterized by tightly curled, fine hair texture present from birth. This gene shows low constraint against loss-of-function variants, consistent with its role in a non-life-threatening hair structure disorder.

ResearchSummary from RefSeq, UniProt

This is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers. [provided by RefSeq, Apr 2014]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.74

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.000

Z-score -0.65

OE 1.19 (0.81–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.38Z-score

OE missense 1.26 (1.14–1.39)

279 obs / 221.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.19 (0.81–1.74)

0≤0.351.4

Missense OE?1.26 (1.14–1.39)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 17 / 14.3Missense obs/exp: 279 / 221.3Syn Z: -0.38

Background carrier burden — how many people carry a rare variant somewhere in KRTAP10-4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

447 rare PASS variants

Rare truncating (LoF)

1 in 1,500

50 rare PASS variants

Rare synonymous (reference)

1 in 130

173 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KRTAP10-4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 80	1 in 1,500
South Asian	~43k	1 in 54	1 in 1,800
Remaining (unassigned)	~30k	1 in 41	1 in 900
European (Finnish)	~27k	1 in 180	none seen
Admixed American	~22k	1 in 49	1 in 1,900
African / African American	~21k	1 in 41	1 in 1,400
East Asian	~20k	1 in 57	1 in 1,200
Ashkenazi Jewish	~13k	1 in 140	none seen
Middle Eastern	~2,884	1 in 88	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓