OSTM1

osteoclastogenesis associated transmembrane protein 1

Basic information

Region (hg38): 6:108029244-108165854

Links

ENSG00000081087 ∙ NCBI:28962 ∙ OMIM:607649 ∙ HGNC:21652 ∙ Uniprot:Q86WC4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive osteopetrosis 5 (Strong), mode of inheritance: AR
• autosomal recessive osteopetrosis 5 (Strong), mode of inheritance: AR
• infantile osteopetrosis with neuroaxonal dysplasia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteopetrosis, autosomal recessive 5	AR	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	Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	3513575; 10325711; 12627228; 15177004; 15108279; 16813530; 17922613; 17985267; 19507210
HSCT has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OSTM1 gene.

• not provided (174 variants)
• Autosomal recessive osteopetrosis 5 (95 variants)
• Inborn genetic diseases (17 variants)
• Osteopetrosis (9 variants)
• not specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OSTM1 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			3	50	2	55
missense			78		2	80
nonsense	4		1			5
start loss						0
frameshift	7	1				8
inframe indel						0
splice donor/acceptor (+/-2bp)	1		1			2
splice region	1		2	2		5
non coding			53	18	34	105
Total	12	1	136	68	38

Variants in OSTM1

This is a list of pathogenic ClinVar variants found in the OSTM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-108041456-T-C		Autosomal recessive osteopetrosis 5	Benign (Jan 13, 2018)
6-108041466-A-C		Autosomal recessive osteopetrosis 5	Benign (Jan 13, 2018)
6-108041505-A-G		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)
6-108041529-T-C		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 12, 2018)
6-108041593-T-G		Autosomal recessive osteopetrosis 5	Likely benign (Jan 13, 2018)
6-108041599-A-G		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)
6-108041725-C-T		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)
6-108041795-A-G		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 12, 2018)
6-108041898-C-T		Autosomal recessive osteopetrosis 5	Benign (Jan 13, 2018)
6-108041927-T-C		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 12, 2018)
6-108041986-T-C		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)
6-108042012-C-T		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)
6-108042016-C-A		Autosomal recessive osteopetrosis 5	Uncertain significance (Mar 23, 2018)
6-108042030-T-C		Autosomal recessive osteopetrosis 5	Benign (Jan 13, 2018)
6-108042078-G-A		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 12, 2018)
6-108042238-C-T		Autosomal recessive osteopetrosis 5	Benign (Jan 12, 2018)
6-108042266-TAC-T		Osteopetrosis	Uncertain significance (Jun 14, 2016)
6-108042267-AC-A		Osteopetrosis	Uncertain significance (Jun 14, 2016)
6-108042268-CAA-C		Osteopetrosis	Uncertain significance (Jun 14, 2016)
6-108042296-TA-T		Osteopetrosis	Uncertain significance (Jun 14, 2016)
6-108042298-A-T		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)
6-108042414-C-T		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)
6-108042414-C-CT		Osteopetrosis	Uncertain significance (Jun 14, 2016)
6-108042419-T-C		Autosomal recessive osteopetrosis 5	Likely benign (Jan 13, 2018)
6-108042421-T-C		Autosomal recessive osteopetrosis 5	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OSTM1	protein_coding	protein_coding	ENST00000193322	6	124446

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0113	0.981	125730	0	6	125736	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	139	180	0.771	0.00000855	2159
Missense in Polyphen		36	60.194	0.59806		727
Synonymous	0.0508	72	72.5	0.992	0.00000320	647
Loss of Function	2.33	6	16.1	0.373	9.12e-7	174

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for osteoclast and melanocyte maturation and function. {ECO:0000250, ECO:0000269|PubMed:21527911}.
• Disease: DISEASE: Osteopetrosis, autosomal recessive 5 (OPTB5) [MIM:259720]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB5 patients manifest primary central nervous system involvement in addition to the classical stigmata of severe bone sclerosis, growth failure, anemia, thrombocytopenia and visual impairment with optic atrophy. {ECO:0000269|PubMed:12627228, ECO:0000269|PubMed:16813530}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.181

Intolerance Scores

• loftool: 0.492
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• pHI: 0.106
• hipred: N
• hipred_score: 0.396
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.734

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ostm1
• Phenotype: vision/eye phenotype; limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: osteoclast differentiation
• Cellular component: lysosomal membrane;cytosol;integral component of membrane