CHAMP1

chromosome alignment maintaining phosphoprotein 1, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 13:114314482-114337626

Previous symbols: [ "C13orf8", "ZNF828" ]

Links

ENSG00000198824 ∙ NCBI:283489 ∙ OMIM:616327 ∙ HGNC:20311 ∙ Uniprot:Q96JM3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features	AD	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	Craniofacial; Musculoskeletal; Neurologic	25533962; 26340335

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHAMP1 gene.

• not provided (16 variants)
• Intellectual disability, autosomal dominant 40 (13 variants)
• CHAMP1-related syndrome (5 variants)
• Inborn genetic diseases (5 variants)
• intellectual disability with severe speech impairment (4 variants)
• Intellectual disability (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHAMP1 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			1	17	6	24
missense			107	38	4	149
nonsense	12	6				18
start loss						0
frameshift	18	8				26
inframe indel			2	2		4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	30	14	110	57	10

Variants in CHAMP1

This is a list of pathogenic ClinVar variants found in the CHAMP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-114323830-AACAG-A		CHAMP1-related disorder	Benign (Mar 28, 2019)
13-114323864-C-T			Likely benign (Dec 01, 2020)
13-114323879-C-T			Uncertain significance (Feb 01, 2024)
13-114323880-G-A		CHAMP1-related disorder • Inborn genetic diseases	Likely benign (Mar 29, 2022)
13-114323887-G-A			Benign/Likely benign (Jul 01, 2024)
13-114323909-G-A		See cases	Uncertain significance (Dec 21, 2022)
13-114323923-A-G		CHAMP1-related disorder	Likely benign (Mar 14, 2019)
13-114323927-G-A			Uncertain significance (May 01, 2024)
13-114323948-A-T		not specified	Uncertain significance (May 19, 2016)
13-114323950-C-G			Uncertain significance (Nov 02, 2019)
13-114323978-G-A		Inborn genetic diseases	Uncertain significance (Aug 20, 2024)
13-114324012-A-G		Intellectual disability, autosomal dominant 40	Uncertain significance (May 06, 2019)
13-114324157-T-A		CHAMP1-related disorder	Likely benign (Mar 14, 2019)
13-114324171-C-G		Inborn genetic diseases	Likely benign (Jun 11, 2024)
13-114324185-C-T		Intellectual disability, autosomal dominant 40	Likely pathogenic (-)
13-114324194-C-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
13-114324206-G-C		Intellectual disability, autosomal dominant 40	Uncertain significance (-)
13-114324216-A-C		Inborn genetic diseases	Uncertain significance (Jun 13, 2024)
13-114324245-C-T			Pathogenic (May 19, 2017)
13-114324248-A-C		Inborn genetic diseases	Uncertain significance (Nov 10, 2024)
13-114324254-G-C			Likely benign (Jan 01, 2024)
13-114324287-ACTC-A			Likely benign (Dec 01, 2023)
13-114324288-C-T			Uncertain significance (Apr 19, 2023)
13-114324291-C-T		Inborn genetic diseases	Uncertain significance (Sep 11, 2024)
13-114324317-C-T		Intellectual disability, autosomal dominant 40	Uncertain significance (Oct 30, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHAMP1	protein_coding	protein_coding	ENST00000361283	1	12809

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00803	125721	0	2	125723	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.140	420	428	0.981	0.0000225	5243
Missense in Polyphen		97	159.83	0.60688		2090
Synonymous	-1.49	174	151	1.15	0.00000742	1682
Loss of Function	4.08	2	23.2	0.0860	0.00000118	336

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore. {ECO:0000269|PubMed:21063390}.
• Disease: DISEASE: Mental retardation, autosomal dominant 40 (MRD40) [MIM:616579]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:26340335}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.175

Intolerance Scores

• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.71

Haploinsufficiency Scores

• pHI: 0.127
• hipred: N
• hipred_score: 0.387
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Champ1

Gene ontology

• Biological process: sister chromatid biorientation;protein localization to kinetochore;protein localization to microtubule;attachment of mitotic spindle microtubules to kinetochore
• Cellular component: condensed chromosome kinetochore;condensed chromosome;nucleus;nucleoplasm;cytoplasm;spindle;Flemming body
• Molecular function: nucleic acid binding;protein binding;metal ion binding