NCAPH

Chr 2AR

non-SMC condensin I complex subunit H

Also known as: BRRN1, CAP-H, CAPH, MCPH23, NCAPH1

This gene encodes a member of the barr gene family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes. The protein encoded by this gene is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization. Alternatively spliced transcript variants encoding different proteins have been described. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

?Microcephaly 23, primary, autosomal recessiveMIM #617985
AR
0
Active trials
34
Pathogenic / LP
195
ClinVar variants
16
Pubs (1 yr)
1.1
Missense Z
0.57
LOEUF
Clinical SummaryNCAPH
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 137 VUS of 195 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 3.61
OE 0.37 (0.240.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.09Z-score
OE missense 0.85 (0.780.93)
353 obs / 415.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.240.57)
00.351.4
Missense OE0.85 (0.780.93)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 14 / 38.1Missense obs/exp: 353 / 415.7Syn Z: 1.05

ClinVar Variant Classifications

195 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic11
VUS137
Likely Benign19
Benign5
23
Pathogenic
11
Likely Pathogenic
137
VUS
19
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
22
0
23
Likely Pathogenic
1
0
10
0
11
VUS
0
105
32
0
137
Likely Benign
0
7
7
5
19
Benign
0
3
1
1
5
Total1116726195

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

View in ClinVar →

NCAPH · protein map & ClinVar variants

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

Gene2Phenotype Curations

NCAPH-related microcephaly

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence