NCAPH

protein-coding

non-SMC condensin I complex subunit H, the group of Condensin I subunits|Kleisins

Gene summary

This gene encodes a member of the barr gene family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes. The protein encoded by this gene is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization. Alternatively spliced transcript variants encoding different proteins have been described. [provided by RefSeq, Jul 2013]

Previous symbols:

BRRN1

MANE transcript

NM_015341.5

Inheritance

ClinVar variants

P:2U:117B:15

Top phenotype

Microcephaly 23, primary, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr2:96,335,766-96,377,091

External References & Databases

Ensembl (ENSG00000121152)

Transcript & Mutation Effects

hg38 • Region Span ~41.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly 23, primary, autosomal recessiveLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054806

Submitter: Labcorp Genetics (formerly Invitae)

microcephaly 23, primary, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054806

Submitter: PanelApp Australia

microcephaly 23, primary, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054806

Submitter: G2P

Clinical Genomic Database (CGD)

Microcephaly 23, 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 NCAPH variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 114

not providedTotal: 11

NCAPH-related disorderTotal: 8

Microcephaly 23, primary, autosomal recessiveTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015341.5. 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	6 clinvar		7
missense	1 clinvar		114 clinvar	7 clinvar	2 clinvar	124
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	1	1	117	13	2	134

Highest pathogenic variant AF is 0.0000034581637

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015341.5	RefSeq	NP_056156.2	18	MANE Select
ENST00000240423.9	Ensembl	ENSP00000240423.4	18	MANE Select
NM_001281710.2	RefSeq	NP_001268639.1	18	Standard
NM_001281711.2	RefSeq	NP_001268640.1	18	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

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

Gene / Model

Organism

Observed Phenotype

ncaph

Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

mitotic chromosome condensation
meiotic chromosome condensation
cell division
female meiosis chromosome separation
positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity

Molecular Function

chromatin binding
protein binding
DNA topoisomerase binding
DNA topoisomerase (ATP-hydrolyzing) activator activity

Cellular Component

condensin complex
nuclear condensin complex
nucleus
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000240423
Coding exons: 18
Length: 38059
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125747
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.09	353	416	0.849	0.0000223	4918
Missense (PolyPhen)		89	134.43	0.66208		1692
Synonymous	1.05	143	160	0.894	0.00000944	1383
Loss of Function	3.61	14	38.1	0.368	0.00000196	456

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000054	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00017	0.00016	rare
Other	0.00049	0.00049	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. {ECO:0000269|PubMed:11136719}.;

Recessive Scores

pRec: 0.123

Intolerance Scores

LoFtool: 0.655
RVIS EVS: -0.31
RVIS percentile EVS: 32.17

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.264

Gene Damage Prediction

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