NCAPD2

protein-coding

non-SMC condensin I complex subunit D2, the group of Armadillo like helical domain containing|Condensin I subunits

Gene summary

Enables histone binding activity. Involved in mitotic chromosome condensation and positive regulation of chromosome condensation. Located in condensed chromosome; cytosol; and nuclear lumen. Part of condensin complex. Implicated in primary autosomal recessive microcephaly 21. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014865.4

Inheritance

ClinVar variants

P:12U:243B:51

Top phenotype

Microcephaly 21, primary, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr12:6,493,356-6,531,955

External References & Databases

Ensembl (ENSG00000010292)

Transcript & Mutation Effects

hg38 • Region Span ~38.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly 21, primary, autosomal recessiveLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054804

Submitter: Labcorp Genetics (formerly Invitae)

microcephaly 21, primary, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054804

Submitter: PanelApp Australia

microcephaly 21, primary, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0054804

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Microcephaly 21, primary, autosomal recessiveAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27737959; 28097321

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NCAPD2 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 229

not providedTotal: 52

NCAPD2-related disorderTotal: 23

not specifiedTotal: 20

Microcephaly 21, primary, autosomal recessiveTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014865.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	15 clinvar	7 clinvar	23
missense		1 clinvar	226 clinvar	26 clinvar	3 clinvar	256
nonsense		2 clinvar	5 clinvar			7
start loss						0
frameshift		5 clinvar	2 clinvar			7
splice donor/acceptor (+/-2bp)	2 clinvar	2 clinvar	9 clinvar			13
Total	2	10	243	41	10	306

Highest pathogenic variant AF is 0.00048963947

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014865.4	RefSeq	NP_055680.3	31	MANE Select
ENST00000315579.10	Ensembl	ENSP00000325017.5	31	MANE Select
ENST00000382457.8	Ensembl	ENSP00000371895.4	20	Standard
ENST00000539084.5	Ensembl	ENSP00000438495.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ncapd2	Danio rerio	Structure: head Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

ncapd2

Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

akap95 role in mitosis and chromosome dynamics
Condensation of Prometaphase Chromosomes
Mitotic Prometaphase
M Phase
Cell Cycle

Biological Process

mitotic chromosome condensation
meiotic chromosome condensation
cell division
chromosome separation

Molecular Function

chromatin binding
protein binding
histone binding

Cellular Component

nuclear chromosome
condensed chromosome, centromeric region
condensed chromosome
condensin complex
condensin core heterodimer

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315579
Coding exons: 31
Length: 38600
Individuals with no LoFs: 125535
Homozygous LoFs: 0
Heterozygous LoFs: 213
Defined: 125748
p: 0.000847

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.709	743	799	0.929	0.0000462	9124
Missense (PolyPhen)		189	218.25	0.86599		2560
Synonymous	0.262	288	294	0.981	0.0000149	2826
Loss of Function	4.60	34	77.8	0.437	0.00000447	828

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00093	0.00093	rare
Ashkenazi Jewish	0.0023	0.0023	notable
East Asian	0.00033	0.00033	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00096	0.00096	rare
South Asian	0.00056	0.00056	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain. {ECO:0000269|PubMed:11136719}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.771
RVIS EVS: -0.05
RVIS percentile EVS: 48.95

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.526

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium