TMEM199

transmembrane protein 199, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 17:28357642-28363683

Previous symbols: [ "C17orf32" ]

Links

ENSG00000244045 ∙ NCBI:147007 ∙ OMIM:616815 ∙ HGNC:18085 ∙ Uniprot:Q8N511 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• TMEM199-CDG (Supportive), mode of inheritance: AR
• TMEM199-CDG (Moderate), mode of inheritance: AR
• TMEM199-CDG (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type IIp	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Gastrointestinal; Hematologic; Neurologic	26833330

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM199 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM199 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				7		7
missense		2	34	1	4	41
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				2		2
non coding				9	7	16
Total	1	3	34	17	11

Highest pathogenic variant AF is 0.0000131

Variants in TMEM199

This is a list of pathogenic ClinVar variants found in the TMEM199 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-28357662-CG-C		TMEM199-related disorder	Likely benign (Nov 20, 2019)
17-28357681-CTT-C			Pathogenic (Jul 05, 2022)
17-28357686-C-G		Inborn genetic diseases	Uncertain significance (Feb 10, 2023)
17-28357686-C-T			Uncertain significance (Jul 05, 2022)
17-28357689-G-A			Uncertain significance (Oct 31, 2019)
17-28357690-C-A		Congenital disorders of glycosylation type II • TMEM199-CDG	Likely pathogenic (Oct 23, 2020)
17-28357690-C-T			Uncertain significance (May 08, 2023)
17-28357706-G-A		TMEM199-related disorder	Conflicting classifications of pathogenicity (Jul 22, 2023)
17-28357710-G-C		TMEM199-CDG	Pathogenic (Feb 29, 2016)
17-28357714-T-C			Benign (Nov 06, 2023)
17-28357744-G-A			Uncertain significance (Sep 01, 2022)
17-28357744-G-T			Uncertain significance (Aug 27, 2021)
17-28357762-G-C		TMEM199-CDG • Congenital disorders of glycosylation type II • TMEM199-related disorder	Pathogenic/Likely pathogenic (Aug 12, 2023)
17-28357770-C-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
17-28357780-C-T			Uncertain significance (Oct 13, 2023)
17-28357792-A-C		Inborn genetic diseases	Uncertain significance (Apr 06, 2024)
17-28357808-T-C			Likely benign (Apr 24, 2018)
17-28357813-C-G		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
17-28357821-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
17-28357826-A-G		TMEM199-CDG	Benign/Likely benign (Jan 18, 2024)
17-28357845-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
17-28357847-C-T			Likely benign (Mar 01, 2024)
17-28357882-G-A			Likely pathogenic (Jul 05, 2022)
17-28357891-A-C			Likely benign (Jun 11, 2018)
17-28357891-A-G		TMEM199-related disorder	Likely benign (Aug 19, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM199	protein_coding	protein_coding	ENST00000292114	6	24113

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000199	0.485	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.246	132	124	1.06	0.00000724	1302
Missense in Polyphen		49	49.545	0.98899		510
Synonymous	-0.873	61	52.9	1.15	0.00000300	455
Loss of Function	0.539	8	9.82	0.814	4.19e-7	119

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000247	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.0000981	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. In aerobic conditions, required for intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation. Necessary for endolysosomal acidification and lysosomal degradation (PubMed:28296633). May be involved in Golgi homeostasis (PubMed:26833330). {ECO:0000269|PubMed:26833330, ECO:0000269|PubMed:28296633}.
• Disease: DISEASE: Congenital disorder of glycosylation 2P (CDG2P) [MIM:616829]: A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2P is characterized by mild metabolic dysfunction, primarily affecting the liver. Psychomotor development is normal. {ECO:0000269|PubMed:26833330}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• rvis_EVS: 0.37
• rvis_percentile_EVS: 75.29

Haploinsufficiency Scores

• pHI: 0.184
• hipred: N
• hipred_score: 0.282
• ghis: 0.523

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.575

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem199

Gene ontology

• Biological process: cellular iron ion homeostasis;lysosomal lumen acidification;cellular response to increased oxygen levels;vacuolar proton-transporting V-type ATPase complex assembly;lysosomal protein catabolic process
• Cellular component: lysosome;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;vacuolar proton-transporting V-type ATPase complex;COPI-coated vesicle membrane;endoplasmic reticulum-Golgi intermediate compartment membrane
• Molecular function: protein binding