CHAMP1

Chr 13AD

chromosome alignment maintaining phosphoprotein 1

Also known as: C13orf8, CAMP, CHAMP, MRD40, NEDHILD, ZNF828

NCBI Gene: 283489 ENSG00000198824 UniProt: Q96JM3 OMIM: 616327

CHAMP1 encodes a zinc finger protein required for proper chromosome alignment at metaphase and accurate chromosome segregation during mitosis by maintaining spindle microtubule attachment to kinetochores. Mutations cause autosomal dominant neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features. This represents an autosomal dominant intellectual disability syndrome with early childhood onset affecting neurological development and growth.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a zinc finger protein that functions as a regulator of chromosome segregation in mitosis. The encoded protein is required for correct alignment of chromosomes on the metaphase plate, and plays a role in maintaining the attachment of sister kinetochores to microtubules from opposite spindle poles. Mutations in this gene are associated with an autosomal dominant form of intellectual disability. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.271 OMIM phenotype

Clinical Summary— CHAMP1

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

59 unique Pathogenic / Likely Pathogenic· 169 VUS of 337 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.992

Z-score 4.08

OE 0.09 (0.03–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.14Z-score

OE missense 0.98 (0.91–1.06)

420 obs / 428.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.27)

0≤0.351.4

Missense OE?0.98 (0.91–1.06)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 2 / 23.2Missense obs/exp: 420 / 428.1Syn Z: -1.49

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCHAMP1-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

0.3097th %ile

GOF

0.13100th %ile

LOF

0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 98% of P/LP variants are LoF · LOEUF 0.27

Literature Evidence

LOFUsing a combination of exome sequencing and array-based detection of chromosomal rearrangements, the Deciphering Developmental Disorders Study (2015) examined 1,133 children with severe undiagnosed developmental disorders and their parents. The authors identified 2 patients with neurodevelopmental d1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 25533962 ↗

ClinVar Variant Classifications

337 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38

Likely Pathogenic21

VUS169

Likely Benign88

Benign11

Conflicting4

Pathogenic

Likely Pathogenic

169

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	37	0	1	0	38
Likely Pathogenic	21	0	0	0	21
VUS	1	166	1	1	169
Likely Benign	0	63	0	25	88
Benign	0	3	1	7	11
Conflicting	—				4
Total	59	232	3	33	331

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

113 pathogenic / likely-pathogenic (of 130) ClinVar copy-number / structural variants overlap CHAMP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →