TMEM167A

Summary

TMEM167A (transmembrane protein 167A, HGNC:28330) is a protein-coding gene on chromosome 5q14.2, encoding Protein kish-A (Q8TBQ9). Involved in the early part of the secretory pathway. It is a selective cancer dependency (DepMap: 22.8% of cell lines).

Involved in constitutive secretory pathway. Located in Golgi apparatus.

Source: NCBI Gene 153339 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neonatal diabetes mellitus (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 22 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 22.8% of screened cell lines
• MANE Select transcript: NM_174909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28330
Approved symbol	TMEM167A
Name	transmembrane protein 167A
Location	5q14.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30508, MGC23909, kish
Ensembl gene	ENSG00000174695
Ensembl biotype	protein_coding
OMIM	620000
Entrez	153339

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding_CDS_not_defined, 1 protein_coding, 1 retained_intron

ENST00000502346, ENST00000503892, ENST00000504622, ENST00000509770, ENST00000511118, ENST00000511450

RefSeq mRNA: 1 — MANE Select: NM_174909 NM_174909

CCDS: CCDS34198

Canonical transcript exons

ENST00000502346 — 4 exons

Exon	Start	End
ENSE00002064642	83052846	83057154
ENSE00002088090	83077321	83077394
ENSE00003562201	83065008	83065117
ENSE00003628954	83061877	83061911

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.7610 / max 832.8301, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62355	39.8541	1813
62356	6.2199	1679
62357	0.6871	379

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.83	gold quality
ileal mucosa	UBERON:0000331	97.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.70	gold quality
monocyte	CL:0000576	97.60	gold quality
substantia nigra pars compacta	UBERON:0001965	97.47	gold quality
upper arm skin	UBERON:0004263	97.38	gold quality
left ventricle myocardium	UBERON:0006566	97.37	gold quality
leukocyte	CL:0000738	97.36	gold quality
islet of Langerhans	UBERON:0000006	97.25	gold quality
pigmented layer of retina	UBERON:0001782	97.14	gold quality
kidney epithelium	UBERON:0004819	97.08	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.98	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.87	gold quality
superior vestibular nucleus	UBERON:0007227	96.84	gold quality
cortical plate	UBERON:0005343	96.75	gold quality
decidua	UBERON:0002450	96.72	gold quality
pons	UBERON:0000988	96.70	gold quality
lateral globus pallidus	UBERON:0002476	96.59	gold quality
medulla oblongata	UBERON:0001896	96.48	gold quality
subthalamic nucleus	UBERON:0001906	96.48	gold quality
calcaneal tendon	UBERON:0003701	96.41	gold quality
inferior vagus X ganglion	UBERON:0005363	96.20	gold quality
pancreatic ductal cell	CL:0002079	96.07	gold quality
corpus callosum	UBERON:0002336	95.96	gold quality
corpus epididymis	UBERON:0004359	95.93	gold quality
trigeminal ganglion	UBERON:0001675	95.78	gold quality
myocardium	UBERON:0002349	95.78	gold quality
vermiform appendix	UBERON:0001154	95.77	gold quality
placenta	UBERON:0001987	95.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

244 targeting TMEM167A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AA	99.96	70.64	3753

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• DISCUSSION The results presented here show that kish/TMEM167A, a protein associated with vesicle transport and secretion,also is necessary for glioma growth, both in human cell xenografts and Drosophila models. (PMID:30506943)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem167a	ENSDARG00000035914
mus_musculus	Tmem167	ENSMUSG00000012422
rattus_norvegicus	AC242615.2	ENSRNOG00000062169
rattus_norvegicus	Tmem167a	ENSRNOG00000085236
drosophila_melanogaster	ksh	FBGN0040890
caenorhabditis_elegans		WBGENE00013373

Paralogs (1): TMEM167B (ENSG00000215717)

Protein

Protein identifiers

Protein kish-A — Q8TBQ9 (reviewed: Q8TBQ9)

Alternative names: Transmembrane protein 167, Transmembrane protein 167A

All UniProt accessions (1): Q8TBQ9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the early part of the secretory pathway.

Subcellular location. Golgi apparatus membrane.

Similarity. Belongs to the KISH family.

RefSeq proteins (1): NP_777569* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009653	Ksh1	Family
IPR051523	KISH_domain	Family

Pfam: PF06842

UniProt features (6 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBQ9-F1	66.51	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 147 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_VESICLE_MEDIATED_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_EXOCYTOSIS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_SECRETION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MARSON_BOUND_BY_FOXP3_STIMULATED

GO Biological Process (2): protein secretion (GO:0009306), constitutive secretory pathway (GO:0045054)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
exocytosis	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM167A	FAM162B	Q5T6X4	564
TMEM167A	NPM3	O75607	517
TMEM167A	YPEL5	P62699	502
TMEM167A	USP32	Q8NFA0	484
TMEM167A	GPR162	Q16538	480
TMEM167A	SMCO2	A6NFE2	475
TMEM167A	SCFD1	Q8WVM8	468
TMEM167A	VGLL4	Q14135	459
TMEM167A	RRP36	Q96EU6	430
TMEM167A	TENT5A	Q96IP4	429
TMEM167A	CCDC91	Q7Z6B0	416
TMEM167A	LRRC58	Q96CX6	405
TMEM167A	ORMDL2	Q53FV1	398
TMEM167A	TMEM9	Q9P0T7	397
TMEM167A	WASL	O00401	394
TMEM167A	WDR7	Q9Y4E6	394

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TMEM167A	IER3IP1	psi-mi:“MI:0915”(physical association)	0.560
TMEM167A		psi-mi:“MI:0915”(physical association)	0.370
HADHB	AGRN	psi-mi:“MI:0914”(association)	0.350
TMEM167A	IER3IP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): TMEM167A (Synthetic Lethality), TMEM167A (Two-hybrid), TMEM167A (Affinity Capture-MS), TMEM167A (Two-hybrid), TMEM167A (Proximity Label-MS), TMEM167A (Proximity Label-MS), TMEM167A (Affinity Capture-RNA), TMEM167A (Affinity Capture-RNA), TMEM167A (Proximity Label-MS), TMEM167A (Affinity Capture-MS), TMEM167A (Co-fractionation), TMEM167A (Affinity Capture-RNA), TMEM167A (Affinity Capture-RNA)

ESM2 similar proteins: A0A194XK05, A0A1B4XBI5, A0A8F4NUZ8, A2VDC5, B5G2S6, C0H420, C6Y4B5, G2TRS3, G5EEQ9, J7FJH0, O30088, O30092, O30278, O36388, P07503, P0AAV0, P0AAV1, P0AAV2, P0AAV3, P0AF40, P0AF41, P0AF42, P0DXB3, P11286, P37953, P53089, Q09714, Q148I3, Q197D8, Q28FL7, Q33300, Q5BJC2, Q5RAL1, Q5WG37, Q5ZII6, Q63ZL3, Q66J17, Q6GLZ9, Q7YTM8, Q8NIQ1

Diamond homologs: A2VDC5, B5G2S6, G2TRS3, Q0IIL4, Q148I3, Q28FL7, Q28GL2, Q54HH9, Q5BJC2, Q5RAL1, Q5RAU6, Q5ZII6, Q6AZW1, Q6DE23, Q80X45, Q8TBQ9, Q8TGJ3, Q9CR64, Q9NRX6, Q9VWH8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4848193	NM_174909.5(TMEM167A):c.113G>A (p.Gly38Glu)	Likely pathogenic

SpliceAI

396 predictions. Top by Δscore:

Variant	Effect	Δscore
5:83056971:T:C	donor_gain	1.0000
5:83057006:T:TA	donor_gain	1.0000
5:83057011:T:A	donor_gain	1.0000
5:83065114:CAGA:C	acceptor_gain	1.0000
5:83065118:C:CC	acceptor_gain	1.0000
5:83077318:TA:T	donor_loss	1.0000
5:83077319:A:AC	donor_gain	1.0000
5:83077320:C:CC	donor_gain	1.0000
5:83077626:G:GT	donor_gain	1.0000
5:83061874:TA:T	donor_loss	0.9900
5:83061875:A:AC	donor_gain	0.9900
5:83061876:C:CC	donor_gain	0.9900
5:83061912:C:CC	acceptor_gain	0.9900
5:83061916:A:C	acceptor_gain	0.9900
5:83061921:A:AC	acceptor_gain	0.9900
5:83065003:CAT:C	donor_loss	0.9900
5:83065005:T:TG	donor_loss	0.9900
5:83065006:AC:A	donor_gain	0.9900
5:83065007:C:CA	donor_loss	0.9900
5:83065007:CC:C	donor_gain	0.9900
5:83065113:GCAGA:G	acceptor_gain	0.9900
5:83065114:CAGAC:C	acceptor_gain	0.9900
5:83065116:GA:G	acceptor_gain	0.9900
5:83077597:G:GT	donor_gain	0.9900
5:83077613:GAG:G	donor_gain	0.9900
5:83061869:ACAC:A	donor_loss	0.9800
5:83061870:CACT:C	acceptor_loss	0.9800
5:83061871:ACTTA:A	acceptor_loss	0.9800
5:83061872:CT:C	acceptor_loss	0.9800
5:83061873:TTAC:T	acceptor_loss	0.9800

AlphaMissense

467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:83057133:A:T	V57D	0.999
5:83057154:C:A	G50V	0.999
5:83061877:C:A	G50C	0.999
5:83061877:C:G	G50R	0.999
5:83057109:G:T	A65D	0.998
5:83057120:A:C	C61W	0.998
5:83057121:C:T	C61Y	0.998
5:83057125:A:G	C60R	0.998
5:83057148:C:G	R52P	0.998
5:83057154:C:T	G50D	0.998
5:83061877:C:T	G50S	0.998
5:83061881:T:A	R48S	0.998
5:83061881:T:G	R48S	0.998
5:83061885:G:T	A47D	0.998
5:83061889:A:G	C46R	0.998
5:83065060:A:G	C21R	0.998
5:83057122:A:G	C61R	0.997
5:83057130:G:T	A58E	0.997
5:83057141:A:C	S54R	0.997
5:83057141:A:T	S54R	0.997
5:83057143:T:G	S54R	0.997
5:83061879:A:T	I49N	0.997
5:83061893:C:A	W44C	0.997
5:83061893:C:G	W44C	0.997
5:83061895:A:G	W44R	0.997
5:83061895:A:T	W44R	0.997
5:83061904:C:G	G41R	0.997
5:83065064:A:C	C19W	0.997
5:83065065:C:T	C19Y	0.997
5:83065068:A:T	I18K	0.997

dbSNP variants (sampled 300 via entrez): RS1000085104 (5:83058705 G>A), RS1000204405 (5:83054130 T>A,C), RS1000323602 (5:83064011 C>G), RS1000355717 (5:83070505 G>A), RS1000393598 (5:83062743 G>A), RS1000412827 (5:83057155 CT>C), RS1000465057 (5:83056885 C>T), RS1000471666 (5:83070216 T>C), RS1000564034 (5:83076129 A>C), RS1000742812 (5:83055781 C>G,T), RS1000800769 (5:83067551 C>A,G), RS1000853477 (5:83059434 C>G), RS1001060813 (5:83067112 T>C), RS1001083680 (5:83060057 C>A,T), RS1001129045 (5:83061497 C>G,T)

Disease associations

OMIM: gene MIM:620000 | disease phenotypes: MIM:614231

GenCC curated gene-disease

Disease	Classification	Inheritance
neonatal diabetes mellitus	Limited	Autosomal recessive

Mondo (2): microcephaly, epilepsy, and diabetes syndrome (MONDO:0100328), neonatal diabetes mellitus (MONDO:0016391)

Orphanet (1): Primary microcephaly-epilepsy-permanent neonatal diabetes syndrome (Orphanet:306558)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002540_4	Osteoarthritis biomarkers	1.000000e-06
GCST002595_17	Clozapine-induced agranulocytosis	5.000000e-06
GCST002806_17	Type 2 diabetes	7.000000e-06
GCST003989_30	Chin dimples	1.000000e-12
GCST009391_384	Metabolite levels	3.000000e-06
GCST90011900_55	Serum alkaline phosphatase levels	9.000000e-19

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005890	osteoarthritis biomarker measurement
EFO:0010437	triacylglycerol 58:10 measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2075685	Efficacy	3	fluorouracil;Platinum compounds;radiotherapy	Stomach Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2075685	TMEM167A, XRCC4	3	3.00	1	fluorouracil;Platinum compounds;radiotherapy

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Copper	decreases expression, increases expression, affects binding	2
dicrotophos	decreases expression	1
bufotalin	increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
manganese chloride	increases abundance, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
deguelin	decreases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Benzo(a)pyrene	increases expression	1
Coal	decreases expression, increases abundance	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression, increases abundance	1
T-2 Toxin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Vanadates	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.