NCAPD2

Chr 12AR

non-SMC condensin I complex subunit D2

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

NCBI Gene: 9918ENSG00000010292UniProt: Q15021OMIM: 615638

NCAPD2 encodes a regulatory subunit of the condensin complex that is essential for mitotic chromosome condensation and resolution of DNA catenanes between sister chromatids during cell division. Mutations cause primary autosomal recessive microcephaly 21, reflecting the protein's critical role in neurogenesis where accurate chromosome condensation in neural stem cells affects neuron pool size and cortical development. This gene is highly constrained against loss-of-function variants, indicating its essential cellular function.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.581 OMIM phenotype
Clinical Summary— NCAPD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 240 VUS of 387 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
0.58LOEUF
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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedNCAPD2-related microcephaly with short statureLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6452th %ile
GOF
0.4578th %ile
LOF
0.3357th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

387 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic9
VUS240
Likely Benign37
Benign20
Conflicting5
44
Pathogenic
9
Likely Pathogenic
240
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
6
0
3
0
9
VUS
6
219
15
0
240
Likely Benign
0
22
5
10
37
Benign
0
5
4
11
20
Conflicting
—5
Total142466921355

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

View in ClinVar →

Protein Context — Lollipop Plot

NCAPD2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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
A novel homozygous splice-site variant of NCAPD2 gene identified in two siblings with primary microcephaly: The second case report.
Lin Y et al.·Clin Genet
2019Case report
NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden.
Li Z et al.·Medicine (Baltimore)
2023
Non-SMC condensin I complex subunit D2 (NCAPD2) reveals its prognostic and immunologic features in human cancers.
Dong X et al.·Aging (Albany NY)
2023
NCAPD2 serves as a potential prognostic biomarker for lung adenocarcinoma and promotes cell proliferation, migration, invasion and cell cycle in vitro.
Wu P et al.·Oncol Res
2024
NCAPD2 augments the tumorigenesis and progression of human liver cancer via the PI3K‑Akt‑mTOR signaling pathway.
Gu JX et al.·Int J Mol Med
2024
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