NCAPG2

protein-coding

non-SMC condensin II complex subunit G2, the group of Armadillo like helical domain containing|Condensin II subunits

Gene summary

This gene encodes a protein that belongs to the Condensin2nSMC family of proteins. The encoded protein is a regulatory subunit of the condensin II complex which, along with the condensin I complex, plays a role in chromosome assembly and segregation during mitosis. A similar protein in mouse is required for early development of the embryo. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Previous symbols:

LUZP5

MANE transcript

NM_017760.7

Inheritance

ClinVar variants

P:1U:145B:41

Top phenotype

Kahn-Kahn-Katsanis syndrome

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr7:158,631,169-158,704,804

External References & Databases

Ensembl (ENSG00000146918)

Transcript & Mutation Effects

hg38 • Region Span ~73.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Khan-Khan-Katsanis syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032764

Submitter: ClinGen

The NCAPG2 gene is located on chromosome 7 at 7q36.3 and encodes the non-SMC condensin II complex subunit G2 protein, a regulatory subunit of the condensin-2 complex which is involved in establishing mitotic chromosome architecture and in maintaining the physical rigidity of the chromatid axis. NCAPG2 was first reported in relation to autosomal recessive Khan-Khan-Katsanis syndrome in 2019 (Khan et al., PMID: 30609410). Khan-Khan-Katsanis syndrome is a neurodevelopmental disorder with variable involvement of the ocular, renal, skeletal, and sometimes cardiac systems. Three missense variants that have been reported in two probands in one publication (PMID: 30609410) are included in this curation. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by functional alteration in patient cells and zebrafish morpholino-induced animal models (PMID: 30609410). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date 04.05.2023 (SOP Version 9).

Khan-Khan-Katsanis syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032764

Submitter: Illumina

Khan-Khan-Katsanis syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032764

Submitter: Labcorp Genetics (formerly Invitae)

Khan-Khan-Katsanis syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032764

Submitter: G2P

Khan-Khan-Katsanis syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032764

Submitter: PanelApp Australia

Khan-Khan-Katsanis syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032764

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Kahn-Kahn-Katsanis syndromeAR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 30609410

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NCAPG2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 143

not providedTotal: 33

NCAPG2-related disorderTotal: 32

Khan-Khan-Katsanis syndromeTotal: 19

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017760.7. 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	14 clinvar	3 clinvar	18
missense			136 clinvar	18 clinvar	6 clinvar	160
nonsense		1 clinvar				1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	1	145	32	9	187

Highest pathogenic variant AF is 0.0000013683203

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 86 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017760.7	RefSeq	NP_060230.5	27	MANE Select
ENST00000356309.8	Ensembl	ENSP00000348657.3	27	MANE Select
NM_001281932.2	RefSeq	NP_001268861.1	27	Standard
NM_001281933.2	RefSeq	NP_001268862.1	27	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway
Condensation of Prophase Chromosomes
Mitotic Prophase
M Phase
Cell Cycle

Biological Process

inner cell mass cell proliferation
transcription by RNA polymerase II
cell cycle
erythrocyte differentiation
chromosome condensation

Molecular Function

methylated histone binding
bHLH transcription factor binding
molecular function regulator

Cellular Component

condensin complex
nucleoplasm
membrane
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409423
Coding exons: 27
Length: 73518
Individuals with no LoFs: 124778
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 124813
p: 0.000140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.94	484	620	0.781	0.0000334	7510
Missense (PolyPhen)		122	188.97	0.6456		2329
Synonymous	1.17	206	229	0.901	0.0000129	2128
Loss of Function	5.87	11	60.2	0.183	0.00000287	775

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.00022	0.00020	rare
Ashkenazi Jewish	0.00032	0.00030	rare
East Asian	0.00017	0.00017	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00024	0.00023	rare
Other	0	0.0	absent

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: 0.164

Intolerance Scores

LoFtool: 0.619
RVIS EVS: 1.27
RVIS percentile EVS: 93.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.776

Gene Damage Prediction

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