KRT10

Chr 17ADAR

keratin 10

Also known as: BCIE, BIE, CK10, EHK, EHK2, EHK2A, EHK2B, IHL

NCBI Gene: 3858 ENSG00000186395 UniProt: P13645

This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Ichthyosis histrix, Lambert typeMIM #146600

Epidermolytic hyperkeratosis 2A, autosomal dominantMIM #620150

Epidermolytic hyperkeratosis 2B, autosomal recessiveMIM #620707

Ichthyosis with confettiMIM #609165

Ichthyosis, annular epidermolytic 1MIM #607602

Active trials

Pathogenic / LP

270

ClinVar variants

Pubs (1 yr)

0.3

Missense Z

0.62

LOEUF

Clinical Summary— KRT10

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

48 Pathogenic / Likely Pathogenic· 104 VUS of 270 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.62LOEUF

pLI 0.003

Z-score 3.00

OE 0.36 (0.21–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.25Z-score

OE missense 0.96 (0.87–1.06)

280 obs / 292.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.21–0.62)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.87–1.06)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18

0≤1.21.6

LoF obs/exp: 9 / 25.3Missense obs/exp: 280 / 292.2Syn Z: -1.56

ClinVar Variant Classifications

270 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38

Likely Pathogenic10

VUS104

Likely Benign66

Benign44

Conflicting8

Pathogenic

Likely Pathogenic

104

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	18	10	0	38
Likely Pathogenic	2	7	1	0	10
VUS	3	86	15	0	104
Likely Benign	0	13	17	36	66
Benign	1	11	24	8	44
Conflicting	—				8
Total	16	135	67	44	270

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

View in ClinVar →

Protein Context — Lollipop Plot

KRT10 · protein map & ClinVar variants

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

Gene2Phenotype Curations

KRT10-related ichthyosiform erythroderma, bullous

definitive

ADDominant NegativeAltered Gene Product Structure

Skin

G2P ↗

KRT10-related ichthyosis, cyclic with epidermolytic hyperkeratosis

definitive

ADDominant NegativeAltered Gene Product Structure

Skin

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

KERATIN 10, TYPE I; KRT10

MIM #148080 · *

?Ichthyosis histrix, Lambert type

MIM #146600