NCAPH2

Chr 22

non-SMC condensin II complex subunit H2

Also known as: CAPH2

NCBI Gene: 29781 ENSG00000025770 UniProt: Q6IBW4 OMIM: 611230

The NCAPH2 protein is a regulatory subunit of the condensin-2 complex that ensures proper mitotic chromosome condensation and organization, particularly critical during neurogenesis for accurate cell division in neural stem cells. Mutations cause microcephaly and developmental delay with autosomal recessive inheritance. This gene is highly intolerant to loss-of-function variants, reflecting its essential role in neurodevelopment.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes one of the non-SMC subunits of the condensin II complex. This complex plays an essential role in mitotic chromosome assembly. Alternate splicing of this gene results in multiple transcript variants.[provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

LOEUF 0.56

Clinical Summary— NCAPH2

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

50 unique Pathogenic / Likely Pathogenic· 282 VUS of 556 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.000

Z-score 3.66

OE 0.35 (0.23–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.18Z-score

OE missense 0.97 (0.89–1.06)

346 obs / 355.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.23–0.56)

0≤0.351.4

Missense OE?0.97 (0.89–1.06)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 13 / 37.1Missense obs/exp: 346 / 355.3Syn Z: -2.66

ClinVar Variant Classifications

556 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25

Likely Pathogenic25

VUS282

Likely Benign165

Benign8

Conflicting26

Pathogenic

Likely Pathogenic

282

VUS

165

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	22	3	0	0	25
Likely Pathogenic	22	3	0	0	25
VUS	4	276	0	2	282
Likely Benign	0	8	1	156	165
Benign	0	3	1	4	8
Conflicting	—				26
Total	48	293	2	162	531

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

View in ClinVar →

146 pathogenic / likely-pathogenic (of 166) ClinVar copy-number / structural variants overlap NCAPH2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →