TMEM165

transmembrane protein 165, the group of Solute carrier family 64

Basic information

Region (hg38): 4:55395957-55453397

Links

ENSG00000134851 ∙ NCBI:55858 ∙ OMIM:614726 ∙ HGNC:30760 ∙ Uniprot:Q9HC07 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• TMEM165-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• TMEM165-congenital disorder of glycosylation (Limited), mode of inheritance: AR
• TMEM165-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• TMEM165-congenital disorder of glycosylation (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type IIk	AR	General	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Craniofacial; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	22683087; 23430531
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM165 gene.

• TMEM165-congenital_disorder_of_glycosylation (120 variants)
• not_specified (38 variants)
• not_provided (16 variants)
• TMEM165-related_disorder (5 variants)
• Aganglionic_megacolon (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM165 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018475.5. 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				40	1	41
missense	2	1	74			77
nonsense	1	1				2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	2	74	40	1

Highest pathogenic variant AF is 0.000016108766

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM165	protein_coding	protein_coding	ENST00000381334	6	57441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.283	0.712	125732	0	13	125745	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.37	117	167	0.702	0.00000853	2039
Missense in Polyphen		34	69.036	0.4925		770
Synonymous	0.469	59	63.8	0.925	0.00000336	687
Loss of Function	2.46	3	12.3	0.244	6.01e-7	168

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000440
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a calcium/proton transporter involved in calcium and in lysosomal pH homeostasis. Therefore, it may play an indirect role in protein glycosylation. {ECO:0000269|PubMed:22683087, ECO:0000269|PubMed:23569283}.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.0809
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

• pHI: 0.110
• hipred: Y
• hipred_score: 0.673
• ghis: 0.640

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem165
• Phenotype: vision/eye phenotype; hematopoietic system phenotype

Zebrafish Information Network

• Gene name: tmem165
• Affected structure: chondrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein N-linked glycosylation;cellular calcium ion homeostasis;Golgi calcium ion transport;regulation of lysosomal lumen pH
• Cellular component: lysosomal membrane;Golgi apparatus;endosome membrane;integral component of membrane;early endosome membrane;late endosome membrane;trans-Golgi network membrane;intracellular membrane-bounded organelle