TMEM64

transmembrane protein 64

Basic information

Region (hg38): 8:90621995-90791632

Links

ENSG00000180694 ∙ NCBI:169200 ∙ ∙ HGNC:25441 ∙ Uniprot:Q6YI46 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM64 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM64 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						0
missense			22			22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	22	0	0

Variants in TMEM64

This is a list of pathogenic ClinVar variants found in the TMEM64 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-90625696-G-A		not specified	Uncertain significance (Nov 17, 2022)
8-90625856-T-C		not specified	Uncertain significance (Sep 14, 2022)
8-90631565-A-C		not specified	Uncertain significance (May 30, 2024)
8-90631617-G-T		not specified	Uncertain significance (Jan 02, 2024)
8-90631619-G-A		not specified	Uncertain significance (Jan 26, 2022)
8-90631634-G-C		not specified	Uncertain significance (Jul 30, 2023)
8-90631689-G-A		not specified	Uncertain significance (Aug 17, 2022)
8-90645158-C-T		not specified	Uncertain significance (Apr 09, 2024)
8-90645191-C-T		not specified	Uncertain significance (Jan 09, 2024)
8-90645281-C-A		not specified	Uncertain significance (Apr 27, 2024)
8-90645304-C-T		not specified	Uncertain significance (Apr 19, 2023)
8-90645310-A-G		not specified	Uncertain significance (Jan 03, 2024)
8-90645313-A-G		not specified	Uncertain significance (Aug 12, 2021)
8-90645566-G-A		not specified	Uncertain significance (Jan 22, 2024)
8-90645686-C-G		not specified	Uncertain significance (Jun 17, 2024)
8-90645694-T-C		not specified	Uncertain significance (Apr 26, 2024)
8-90645701-A-G		not specified	Uncertain significance (Apr 18, 2023)
8-90645754-C-A		not specified	Uncertain significance (Oct 02, 2023)
8-90645755-C-A		not specified	Uncertain significance (Oct 02, 2023)
8-90645755-C-T		not specified	Uncertain significance (Dec 06, 2022)
8-90645764-G-A		not specified	Uncertain significance (Jan 03, 2024)
8-90645776-C-G		not specified	Uncertain significance (Mar 01, 2023)
8-90645778-G-T		not specified	Uncertain significance (May 30, 2023)
8-90645820-G-A		not specified	Uncertain significance (Mar 23, 2023)
8-90645830-C-T		not specified	Uncertain significance (May 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM64	protein_coding	protein_coding	ENST00000458549	3	169638

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.490	0.506	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.622	153	176	0.868	0.00000802	2370
Missense in Polyphen		53	70.074	0.75634		797
Synonymous	0.00420	76	76.0	0.999	0.00000349	885
Loss of Function	2.39	2	10.3	0.194	5.03e-7	120

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)	0.0000267	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Positively regulates TNFSF11-induced osteoclast differentiation. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with SERCA2 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation. Negatively regulates osteoblast differentiation and positively regulates adipocyte differentiation via modulation of the canonical Wnt signaling pathway. Mediates the switch in lineage commitment to osteogenesis rather than to adipogenesis in mesenchymal stem cells by negatively regulating the expression, activity and nuclear localization of CTNNB1. {ECO:0000250|UniProtKB:Q3U145}.

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.169
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.429
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0765

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem64
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; immune system phenotype; skeleton phenotype

Gene ontology

• Biological process: regulation of ATPase activity;positive regulation of fat cell differentiation;negative regulation of osteoblast differentiation;positive regulation of osteoclast differentiation;positive regulation of bone resorption;regulation of cytosolic calcium ion concentration;negative regulation of canonical Wnt signaling pathway
• Cellular component: endoplasmic reticulum;integral component of membrane