CHAMP1

Chr 13AD

chromosome alignment maintaining phosphoprotein 1

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

NCBI Gene: 283489ENSG00000198824UniProt: Q96JM3

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]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic featuresMIM #616579
AD
293
ClinVar variants
78
Pathogenic / LP
0.99
pLI score· haploinsufficient
1
Active trials
Clinical Summary— CHAMP1
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
78 Pathogenic / Likely Pathogenic· 133 VUS of 293 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.14Z-score
OE missense 0.98 (0.91–1.06)
420 obs / 428.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.03–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 2 / 23.2Missense obs/exp: 420 / 428.1Syn Z: -1.49

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic12
VUS133
Likely Benign72
Benign9
Conflicting1
66
Pathogenic
12
Likely Pathogenic
133
VUS
72
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
58
0
66
Likely Pathogenic
6
0
6
0
12
VUS
1
119
13
0
133
Likely Benign
0
46
2
24
72
Benign
0
3
1
5
9
Conflicting
—1
Total151688029293

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

View in ClinVar →

Protein Context — Lollipop Plot

CHAMP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CHAMP1-related neurodevelopmental disorder

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features

MIM #616579

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CHAMP1-related disorders: pathomechanisms triggered by different genomic alterations define distinct nosological categories.
Amenta S et al.·Eur J Hum Genet
2023Review
CHAMP1-Related Disorder: Sharing 20 Years of thorough Clinical Follow-Up and Review of the Literature.
Abi Raad S et al.·Genes (Basel)
2023Review
CHAMP1 disorder is associated with a complex neurobehavioral phenotype including autism, ADHD, repetitive behaviors and sensory symptoms.
Levy T et al.·Hum Mol Genet
2022
CHAMP1 is an essential regulator for human myoblast fusion and muscle development.
Zhang H et al.·Nat Commun
2026
[Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene].
Xu J et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Review
Prospective phenotyping of CHAMP1 disorder indicates that coding mutations may not act through haploinsufficiency.
Levy T et al.·Hum Genet
2023
Neurodevelopmental phenotypes in individuals with pathogenic variants in CHAMP1.
Garrity M et al.·Cold Spring Harb Mol Case Stud
2021
Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts.
Marangoni M et al.·Genet Med
2022Cohort
De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability.
Isidor B et al.·Hum Mutat
2016
The rare 13q33-q34 microdeletions: eight new patients and review of the literature.
Sagi-Dain L et al.·Hum Genet
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools