NCAPD2

Chr 12AR

non-SMC condensin I complex subunit D2

Also known as: CAP-D2, CNAP1, MCPH21, hCAP-D2

NCBI Gene: 9918ENSG00000010292UniProt: Q15021

Enables histone binding activity. Involved in mitotic chromosome condensation and positive regulation of chromosome condensation. Located in several cellular components, including condensed chromosome; microtubule organizing center; and nuclear lumen. Part of condensin complex. Implicated in primary autosomal recessive microcephaly 21. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Microcephaly 21, primary, autosomal recessiveMIM #617983
AR
0
Active trials
51
Pathogenic / LP
351
ClinVar variants
10
Pubs (1 yr)
0.7
Missense Z
0.58
LOEUF
Clinical Summary— NCAPD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 238 VUS of 351 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 4.60
OE 0.44 (0.33–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.71Z-score
OE missense 0.93 (0.87–0.99)
743 obs / 799.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.33–0.58)
0≤0.351.4
Missense OE0.93 (0.87–0.99)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 34 / 77.8Missense obs/exp: 743 / 799.4Syn Z: 0.26
DN
DN
0.6452th %ile
GOF
0.4578th %ile
LOF
0.3357th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

351 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic7
VUS238
Likely Benign37
Benign20
Conflicting5
44
Pathogenic
7
Likely Pathogenic
238
VUS
37
Likely Benign
20
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
42
0
44
Likely Pathogenic
4
0
3
0
7
VUS
3
216
19
0
238
Likely Benign
0
22
5
10
37
Benign
0
5
4
11
20
Conflicting
—5
Total92437321351

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

View in ClinVar →

NCAPD2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NCAPD2-related microcephaly with short stature

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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients