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.

not_specified (53 variants)

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. These statistics are base on transcript: NM_001008495.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			53 clinvar			53
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	0	0

Loading clinvar variants...

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
Molecular function