TMEM240

protein-coding

transmembrane protein 240

Gene summary

This gene encodes a transmembrane-domain containing protein found in the brain and cerebellum. Mutations in this gene result in spinocerebellar ataxia 21. [provided by RefSeq, Dec 2014]

Previous symbols:

C1orf70
SCA21

MANE transcript

NM_001114748.2

Inheritance

ClinVar variants

P:6U:75B:48

Top phenotype

Spinocerebellar ataxia 21

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr1:1,534,778-1,540,624

External References & Databases

Ensembl (ENSG00000205090)

Transcript & Mutation Effects

hg38 • Region Span ~5.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spinocerebellar ataxia type 21STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011833

Submitter: Genomics England PanelApp

spinocerebellar ataxia type 21STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011833

Submitter: PanelApp Australia

spinocerebellar ataxia type 21DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011833

Submitter: G2P

spinocerebellar ataxia type 21SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011833

Submitter: Orphanet

spinocerebellar ataxia type 21MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0011833

Submitter: Ambry Genetics

spinocerebellar ataxia type 21STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011833

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spinocerebellar ataxia 21AD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 11160961; 25070513

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM240 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 117

Inborn genetic diseasesTotal: 39

not specifiedTotal: 25

Spinocerebellar ataxia type 21Total: 15

TMEM240-related disorderTotal: 14

Neurodevelopmental disorderTotal: 1

Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndromeTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001114748.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				34 clinvar	4 clinvar	38
missense	1 clinvar	4 clinvar	68 clinvar	10 clinvar		83
nonsense	1 clinvar		2 clinvar			3
start loss			1 clinvar			1
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	4	75	44	4	129

Highest pathogenic variant AF is 0.000062565465

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001114748.2	RefSeq	NP_001108220.1	4	MANE Select
ENST00000378733.9	Ensembl	ENSP00000368007.4	4	MANE Select
ENST00000624426.1	Ensembl	ENSP00000485135.1	2	Standard
ENST00000624426.2	Ensembl	ENSP00000485135.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane
cell junction
synaptic membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378733
Coding exons: 4
Length: 5280
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.55	62	107	0.579	0.00000734	1125
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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