NCAPD3

Chr 11

non-SMC condensin II complex subunit D3

Also known as: CAP-D3, CAPD3, MCPH22, hCAP-D3, hHCP-6, hcp-6

NCBI Gene: 23310 ENSG00000151503 UniProt: P42695

NCAPD3 encodes a regulatory subunit of the condensin-2 complex that establishes mitotic chromosome architecture and is essential for chromosome condensation and decatenation during cell division, particularly in neuronal stem cells during early neurogenesis. Mutations cause primary microcephaly 22, an autosomal recessive disorder affecting brain development and cortex size. The gene is highly constrained against loss-of-function variants (LOEUF 0.489), reflecting its essential role in normal neurodevelopment.

ResearchSummary from RefSeq, OMIM, UniProt

Condensin complexes I and II play essential roles in mitotic chromosome assembly and segregation. Both condensins contain 2 invariant structural maintenance of chromosome (SMC) subunits, SMC2 (MIM 605576) and SMC4 (MIM 605575), but they contain different sets of non-SMC subunits. NCAPD3 is 1 of 3 non-SMC subunits that define condensin II (Ono et al., 2003 [PubMed 14532007]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.49

Clinical Summary— NCAPD3

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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

11 unique Pathogenic / Likely Pathogenic· 260 VUS of 393 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.000

Z-score 5.40

OE 0.36 (0.27–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.73Z-score

OE missense 1.07 (1.01–1.13)

876 obs / 817.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.36 (0.27–0.49)

0≤0.351.4

Missense OE?1.07 (1.01–1.13)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 30 / 83.1Missense obs/exp: 876 / 817.4Syn Z: -3.36

ClinVar Variant Classifications

393 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic6

VUS260

Likely Benign58

Benign21

Conflicting3

Pathogenic

Likely Pathogenic

260

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	1	0	5
Likely Pathogenic	6	0	0	0	6
VUS	4	255	1	0	260
Likely Benign	0	19	11	28	58
Benign	0	12	4	5	21
Conflicting	—				3
Total	13	287	17	33	353

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

View in ClinVar →

93 pathogenic / likely-pathogenic (of 108) ClinVar copy-number / structural variants overlap NCAPD3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →