NCAPH

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

Basic information

Region (hg38): 2:96335765-96377091

Previous symbols: [ "BRRN1" ]

Links

ENSG00000121152 ∙ NCBI:23397 ∙ OMIM:602332 ∙ HGNC:1112 ∙ Uniprot:Q15003 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 23, primary, autosomal recessive (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 23, primary, autosomal recessive	AR	General	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	Neurologic	27737959

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NCAPH gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCAPH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense			33	4	3	40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	3	1	5
non coding				2		2
Total	0	1	33	10	4

Variants in NCAPH

This is a list of pathogenic ClinVar variants found in the NCAPH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-96335829-G-A		NCAPH-related disorder	Likely benign (Feb 22, 2019)
2-96335849-G-C		Microcephaly 23, primary, autosomal recessive	Likely pathogenic (Mar 29, 2024)
2-96341637-TC-T			Uncertain significance (Jun 01, 2021)
2-96341719-G-T		not specified	Uncertain significance (Mar 28, 2023)
2-96341721-G-T		NCAPH-related disorder	Likely benign (Aug 20, 2019)
2-96341726-C-G		not specified	Uncertain significance (Sep 27, 2022)
2-96341726-C-T		not specified	Uncertain significance (May 23, 2023)
2-96341747-C-T		not specified	Uncertain significance (Apr 04, 2023)
2-96341768-C-G		not specified	Uncertain significance (Jun 12, 2023)
2-96341770-C-G		not specified	Uncertain significance (Jan 23, 2023)
2-96341827-C-T		not specified	Uncertain significance (Jul 05, 2023)
2-96341861-A-T		not specified	Uncertain significance (Apr 29, 2024)
2-96341870-G-A		not specified	Likely benign (Sep 27, 2021)
2-96341891-G-A		not specified	Uncertain significance (Sep 14, 2022)
2-96341893-A-G		not specified	Uncertain significance (Jun 13, 2024)
2-96342072-A-G		NCAPH-related disorder	Benign (Aug 28, 2019)
2-96342766-C-T		not specified	Uncertain significance (Dec 01, 2022)
2-96343223-G-A		not specified	Uncertain significance (Mar 25, 2024)
2-96343232-G-A		not specified	Uncertain significance (Mar 29, 2024)
2-96343234-T-C		NCAPH-related disorder	Likely benign (Dec 31, 2019)
2-96343301-G-C		not specified	Uncertain significance (Aug 04, 2021)
2-96344101-T-G		NCAPH-related disorder	Likely benign (May 16, 2019)
2-96344170-A-G			Benign (Oct 17, 2017)
2-96351837-C-T		not specified	Uncertain significance (Jan 20, 2023)
2-96351838-C-T		Microcephaly 23, primary, autosomal recessive	Pathogenic (May 17, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCAPH	protein_coding	protein_coding	ENST00000240423	18	38059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000801	1.00	125714	0	33	125747	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	353	416	0.849	0.0000223	4918
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000871	0.0000871
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000568	0.0000544
Finnish	0.000325	0.000323
European (Non-Finnish)	0.000133	0.000123
Middle Eastern	0.0000568	0.0000544
South Asian	0.000165	0.000163
Other	0.000490	0.000489

dbNSFP

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}.
• Pathway: Condensation of Prometaphase Chromosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Aurora B signaling (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.655
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.17

Haploinsufficiency Scores

• pHI: 0.640
• hipred: Y
• hipred_score: 0.765
• ghis: 0.657

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.264

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ncaph
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Zebrafish Information Network

• Gene name: ncaph
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: mitotic chromosome condensation;meiotic chromosome condensation;cell division;female meiosis chromosome separation;positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity
• Cellular component: condensin complex;nuclear condensin complex;nucleus;cytosol;membrane
• Molecular function: chromatin binding;protein binding;DNA topoisomerase binding;DNA topoisomerase (ATP-hydrolyzing) activator activity