ALMS1

ALMS1 centrosome and basal body associated protein

Basic information

Region (hg38): 2:73385757-73625166

Links

ENSG00000116127 ∙ NCBI:7840 ∙ OMIM:606844 ∙ HGNC:428 ∙ Uniprot:Q8TCU4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Alstrom syndrome (Strong), mode of inheritance: AR
• Alstrom syndrome (Definitive), mode of inheritance: AR
• Alstrom syndrome (Strong), mode of inheritance: AR
• Alstrom syndrome (Strong), mode of inheritance: AR
• Alstrom syndrome (Supportive), mode of inheritance: AR
• Alstrom syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alstrom syndrome	AR	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Ophthalmologic; Renal	The condition may be recognizable from early manifestations (eg, related to visual loss), but dilated or restricted cardiomyopathy is common, and measures to decrease related morbidity and mortality may be beneficial; Management related to other sequelae, such as endocrine (eg, diabetes mellitus), renal, and hepatic manifestations, may also be beneficial; Recognition of hearing impairment can allow interventions related to speech and language development	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Ophthalmologic; Renal	13649370; 5824738; 3766665; 3687707; 2231654; 1746604; 8418611; 8488920; 8636816; 9066877; 9409865; 9663233; 11343329; 11941369; 11941370; 17594715; 17850632; 22043170; 21522186; 20301444; 25864795

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALMS1 gene.

• Alstrom syndrome (5009 variants)
• Cardiovascular phenotype (1483 variants)
• not provided (757 variants)
• not specified (447 variants)
• Monogenic diabetes (70 variants)
• ALMS1-related condition (60 variants)
• Inborn genetic diseases (46 variants)
• Retinal dystrophy (25 variants)
• Leber congenital amaurosis (6 variants)
• Retinitis pigmentosa (5 variants)
• Hearing impairment (4 variants)
• Bardet-Biedl syndrome (3 variants)
• Nephrotic syndrome (2 variants)
• See cases (2 variants)
• Intellectual disability (2 variants)
• Leukodystrophy;Stage 5 chronic kidney disease;Visual impairment;Hearing impairment (1 variants)
• Retinal dystrophy, early-onset severe (1 variants)
• Stickler syndrome (1 variants)
• Abnormality of the eye (1 variants)
• Complete trisomy 21 syndrome (1 variants)
• Occult maculopathy (1 variants)
• Cone-rod dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALMS1 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			98	1415	17	1530
missense	4	4	2484	41	26	2559
nonsense	190	108	3			301
start loss		3	2			5
frameshift	227	124	7	1	3	362
inframe indel			125	13	4	142
splice donor/acceptor (+/-2bp)	6	38	3			47
splice region		3	68	55	4	130
non coding		4	49	211	30	294
Total	427	281	2771	1681	80

Highest pathogenic variant AF is 0.0000460

Variants in ALMS1

This is a list of pathogenic ClinVar variants found in the ALMS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-73385762-G-A		Alstrom syndrome	Uncertain significance (Dec 08, 2021)
2-73385778-A-G		Alstrom syndrome	Uncertain significance (Jan 12, 2018)
2-73385791-A-G		Alstrom syndrome	Uncertain significance (Jan 12, 2018)
2-73385805-C-T		Alstrom syndrome	Uncertain significance (Aug 23, 2021)
2-73385816-C-T		Alstrom syndrome	Uncertain significance (Jan 13, 2018)
2-73385821-C-T		Alstrom syndrome	Uncertain significance (Jan 13, 2018)
2-73385823-TC-T		Alstrom syndrome	Uncertain significance (Jun 14, 2016)
2-73385824-C-G		not specified	Likely benign (Oct 27, 2016)
2-73385823-T-TCCC			Likely benign (Oct 27, 2017)
2-73385828-CCCT-C		Alstrom syndrome	Likely benign (Jun 14, 2016)
2-73385828-C-CCCT			Benign (Dec 05, 2019)
2-73385848-C-T		not specified	Likely benign (Nov 20, 2017)
2-73385849-G-A		Alstrom syndrome	Uncertain significance (Aug 31, 2021)
2-73385850-C-T		Alstrom syndrome	Uncertain significance (Jan 04, 2018)
2-73385853-A-G		Alstrom syndrome	Uncertain significance (Mar 31, 2017)
2-73385857-C-G		Alstrom syndrome	Uncertain significance (May 15, 2017)
2-73385857-CGAGACACCAA-C		Cardiovascular phenotype	Likely benign (Aug 04, 2020)
2-73385860-G-A		Alstrom syndrome	Uncertain significance (Sep 22, 2017)
2-73385860-G-GA		Alstrom syndrome	Uncertain significance (May 15, 2018)
2-73385862-C-T		Alstrom syndrome	Uncertain significance (May 03, 2018)
2-73385867-ACATGGAGCC-A		Alstrom syndrome	Likely pathogenic (Sep 20, 2017)
2-73385868-C-T		Alstrom syndrome	Uncertain significance (Nov 09, 2017)
2-73385869-A-C		Alstrom syndrome	Uncertain significance (Nov 02, 2022)
2-73385869-A-G		Alstrom syndrome	Uncertain significance (Jun 27, 2022)
2-73385870-T-G		Alstrom syndrome	Likely pathogenic (Apr 28, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALMS1	protein_coding	protein_coding	ENST00000264448	23	225035

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.50e-60	0.00613	125607	0	141	125748	0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.99	2437	2.06e+3	1.19	0.000104	27075
Missense in Polyphen		670	594.06	1.1278		8851
Synonymous	-3.05	868	761	1.14	0.0000390	8368
Loss of Function	2.89	114	152	0.748	0.00000820	2008

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00106	0.00103
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000612	0.000598
Finnish	0.000280	0.000277
European (Non-Finnish)	0.000705	0.000695
Middle Eastern	0.000612	0.000598
South Asian	0.000564	0.000555
Other	0.000355	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in PCM1-dependent intracellular transport. Required, directly or indirectly, for the localization of NCAPD2 to the proximal ends of centrioles. Required for proper formation and/or maintenance of primary cilia (PC), microtubule-based structures that protrude from the surface of epithelial cells. {ECO:0000269|PubMed:17954613}.
• Disease: DISEASE: Alstrom syndrome (ALMS) [MIM:203800]: A rare autosomal recessive disorder characterized by progressive cone-rod retinal dystrophy, neurosensory hearing loss, early childhood obesity and diabetes mellitus type 2. Dilated cardiomyopathy, acanthosis nigricans, male hypogonadism, hypothyroidism, developmental delay and hepatic dysfunction can also be associated with the syndrome. {ECO:0000269|PubMed:11941369, ECO:0000269|PubMed:11941370}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.953
• rvis_EVS: 2.29
• rvis_percentile_EVS: 98.28

Haploinsufficiency Scores

• pHI: 0.0768
• hipred: N
• hipred_score: 0.132
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0421

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Alms1
• Phenotype: reproductive system phenotype; pigmentation phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; hearing/vestibular/ear phenotype; 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); vision/eye phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: alms1
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;regulation of G2/M transition of mitotic cell cycle;endosomal transport;regulation of centriole replication;regulation of stress fiber assembly;ciliary basal body-plasma membrane docking;positive regulation of cold-induced thermogenesis
• Cellular component: spindle pole;centrosome;centriole;cytosol;cilium
• Molecular function: molecular_function;protein binding;alpha-actinin binding