NCAPD3

protein-coding

non-SMC condensin II complex subunit D3, the group of Condensin II subunits|Armadillo like helical domain containing

Gene summary

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]

MANE transcript

NM_015261.3

Inheritance

ClinVar variants

P:10U:270B:73

Top phenotype

Microcephaly 22, primary, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr11:134,150,113-134,225,504

External References & Databases

Ensembl (ENSG00000151503)

Transcript & Mutation Effects

hg38 • Region Span ~75.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly 22, primary, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0054805

Submitter: PanelApp Australia

microcephaly 22, primary, autosomal recessiveLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054805

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive primary microcephalySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016660

Submitter: Orphanet

Clinical Genomic Database (CGD)

Microcephaly 22, 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

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NCAPD3 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 293

NCAPD3-related disorderTotal: 58

not providedTotal: 33

Microcephaly 22, primary, autosomal recessiveTotal: 18

Intellectual disabilityTotal: 6

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015261.3. 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			6 clinvar	34 clinvar	4 clinvar	44
missense	1 clinvar		258 clinvar	27 clinvar	8 clinvar	294
nonsense		3 clinvar	1 clinvar			4
start loss						0
frameshift	2 clinvar	2 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	4 clinvar			6
Total	4	6	270	61	12	353

Highest pathogenic variant AF is 0.000025402978

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015261.3	RefSeq	NP_056076.1	35	MANE Select
ENST00000534548.7	Ensembl	ENSP00000433681.3	35	MANE Select
NM_001372065.1	RefSeq	NP_001358994.1	34	Standard
NM_001372068.1	RefSeq	NP_001358997.1	35	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Condensation of Prophase Chromosomes
Mitotic Prophase
M Phase
Cell Cycle
Cell Cycle, Mitotic

Biological Process

mitotic chromosome condensation
meiotic chromosome condensation
cell division
chromosome separation

Molecular Function

chromatin binding
protein binding
methylated histone binding
histone binding

Cellular Component

condensed chromosome, centromeric region
nuclear condensin complex
nucleoplasm
membrane
nuclear pericentric heterochromatin

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000534548
Coding exons: 35
Length: 75335
Individuals with no LoFs: 125660
Homozygous LoFs: 0
Heterozygous LoFs: 88
Defined: 125748
p: 0.000350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.728	876	817	1.07	0.0000445	9807
Missense (PolyPhen)		136	178.05	0.76383		2239
Synonymous	-3.36	396	320	1.24	0.0000186	2863
Loss of Function	5.40	30	83.1	0.361	0.00000438	985

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00038	0.00038	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00036	0.00036	rare
South Asian	0.00030	0.00029	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis. {ECO:0000269|PubMed:14532007}.;

Recessive Scores

pRec: 0.0997

Intolerance Scores

LoFtool: 0.733
RVIS EVS: -0.37
RVIS percentile EVS: 28.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.500

Gene Damage Prediction

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