TMEM240

transmembrane protein 240

Basic information

Region (hg38): 1:1534778-1540624

Previous symbols: [ "C1orf70", "SCA21" ]

Links

ENSG00000205090 ∙ NCBI:339453 ∙ OMIM:616101 ∙ HGNC:25186 ∙ Uniprot:Q5SV17 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 21 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 21 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 21 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 21 (Moderate), mode of inheritance: AD
• spinocerebellar ataxia type 21 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 21	AD	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	Neurologic	11160961; 25070513

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM240 gene.

• not_provided (104 variants)
• Inborn_genetic_diseases (36 variants)
• Spinocerebellar_ataxia_type_21 (14 variants)
• not_specified (12 variants)
• TMEM240-related_disorder (10 variants)
• Neurodevelopmental_disorder (1 variants)
• Acute_infantile_liver_failure-cerebellar_ataxia-peripheral_sensory_motor_neuropathy_syndrome (1 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM240 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001114748.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				28	7	35
missense		5	62	9		76
nonsense	1		2			3
start loss			1			1
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	1	5	67	37	7

Highest pathogenic variant AF is 0.000062565465

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM240	protein_coding	protein_coding	ENST00000378733	4	5280

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.229	0.740	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.55	62	107	0.579	0.00000734	1125
Missense in Polyphen		28	54.458	0.51415		544
Synonymous	-0.550	56	51.0	1.10	0.00000397	328
Loss of Function	1.80	2	7.23	0.276	3.15e-7	78

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Spinocerebellar ataxia 21 (SCA21) [MIM:607454]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA21 is characterized by onset in the first decades of life of slowly progressive relatively mild cerebellar ataxia associated with slight extrapyramidal features predominant in older patients and cognitive impairment predominant in younger patients. {ECO:0000269|PubMed:25070513, ECO:0000269|PubMed:29053796}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 0.21
• rvis_percentile_EVS: 67.72

Haploinsufficiency Scores

• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem240

Gene ontology

• Cellular component: integral component of membrane;cell junction;synaptic membrane