ALMS1

Chr 2AR

ALMS1 centrosome and basal body associated protein

Also known as: ALSS

NCBI Gene: 7840ENSG00000116127UniProt: Q8TCU4

This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]

Primary Disease Associations & Inheritance

Alstrom syndromeMIM #203800
AR
569
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ALMS1
🧬
Gene-Disease Validity (ClinGen)
Alstrom syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 281 VUS of 569 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
Tolerant — LoF & missense variants common in population
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.
0.87LOEUF
pLI 0.000
Z-score 2.89
OE 0.75 (0.64–0.87)
Tolerant

Typical tolerance to LoF variation

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.
-2.99Z-score
OE missense 1.19 (1.15–1.23)
2437 obs / 2055.4 exp
Tolerant

Tolerant to missense variation

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.0.75 (0.64–0.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.19 (1.15–1.23)
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.1.14
0≤1.21.6
LoF obs/exp: 114 / 152.5Missense obs/exp: 2437 / 2055.4Syn Z: -3.05

ClinVar Variant Classifications

569 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic18
VUS281
Likely Benign215
Benign3
Conflicting5
47
Pathogenic
18
Likely Pathogenic
281
VUS
215
Likely Benign
3
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
1
19
0
47
Likely Pathogenic
15
1
2
0
18
VUS
0
252
11
18
281
Likely Benign
1
53
28
133
215
Benign
0
0
2
1
3
Conflicting
—5
Total4330762152569

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

View in ClinVar →

Protein Context — Lollipop Plot

ALMS1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ALMS1-related Alstrom syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkinEar
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Alstrom syndrome

MIM #203800

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ALMS1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.
Astuti D et al.·Hum Mutat
2017
A novel variant in ALMS1 in a patient with Alström syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review.
Zhou C et al.·Mol Med Rep
2020Review
Alström syndrome.
Marshall JD et al.·Eur J Hum Genet
2007
CEP76 impairment at the centrosome-cilium interface contributes to a spectrum of ciliopathies.
Khan K et al.·Sci Adv
2025
Characterisation of infantile cardiomyopathy in Alström syndrome using ALMS1 knockout induced pluripotent stem cell derived cardiomyocyte model.
Patel L et al.·Mol Genet Metab
2024Functional
Identification of Novel Genetic Risk Factors for Focal Segmental Glomerulosclerosis in Children: Results From the Chronic Kidney Disease in Children (CKiD) Cohort.
Durand A et al.·Am J Kidney Dis
2023Cohort
Genotype-phenotype associations in Alström syndrome: a systematic review and meta-analysis.
Bea-Mascato B et al.·J Med Genet
2023Meta-analysis
LncRNA ALMS1-IT1 is a novel prognostic biomarker and correlated with immune infiltrates in colon adenocarcinoma.
Lin Y et al.·Medicine (Baltimore)
2022
Identification of ACBP as a potential target in ciliopathic obesity through multi-omics network analysis.
Corral Nieto Y et al.·Nat Commun
2026
Overburden of rare ALMS1 deleterious variants in Chinese early-onset type 2 diabetes with severe insulin resistance.
Zhang S et al.·Diabetes Metab Res Rev
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Alms1 KO Rat: A New Model of Cardiometabolic Syndrome With Spontaneous Hypertension.
Jaykumar AB et al.·Acta Physiol (Oxf)
2026🔓 Open AccessFunctional
Characterisation of a Missense Variant of the Alström Syndrome Centrosome and Basal Body Associated Protein (ALMS1) Gene Associated with Cardiomyopathy Using Induced Pluripotent Stem Cells.
Dargar T et al.·Genes (Basel)
2026
Clinical Presentation of a Child With a Novel ALMS1 Variant Associated With Alström Syndrome and Favorable Response to GLP-1 Receptor Agonist Therapy.
Alvarez G et al.·Am J Med Genet A
2026
Phosphoproteomic profiling highlights CDC42 and CDK2 as key players in the regulation of the TGF-β pathway in ALMS1 and BBS1 knockout models.
Bea-Mascato B et al.·Sci Rep
2025🔓 Open AccessFunctional
Multi-matrix metabolomics in rare monogenic diabetes syndromes: Analysis of oral fluids and serum in carriers of pathogenic variants in the ALMS1/BBS genes.
Zmysłowska-Polakowska E et al.·Comput Struct Biotechnol J
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools