TMEM191B

Summary

TMEM191B (transmembrane protein 191B, HGNC:33600) is a protein-coding gene on chromosome 22q11.21, encoding Transmembrane protein 191B (P0C7N4). It is a selective cancer dependency (DepMap: 20.0% of cell lines).

Predicted to be located in membrane.

Source: NCBI Gene 728229 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total — 2 pathogenic
• Cancer dependency (DepMap): dependent in 20.0% of screened cell lines
• MANE Select transcript: NM_001242313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33600
Approved symbol	TMEM191B
Name	transmembrane protein 191B
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000278558
Ensembl biotype	protein_coding
Entrez	728229

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 retained_intron, 2 protein_coding

ENST00000612978, ENST00000613577, ENST00000614395, ENST00000618859, ENST00000620199, ENST00000621725

RefSeq mRNA: 1 — MANE Select: NM_001242313 NM_001242313

CCDS: CCDS74816

Canonical transcript exons

ENST00000612978 — 9 exons

Exon	Start	End
ENSE00003718187	18529936	18530008
ENSE00003725047	18530156	18530196
ENSE00003732736	18527802	18528276
ENSE00003740163	18529019	18529093
ENSE00003742766	18529441	18529497
ENSE00003744338	18529606	18529724
ENSE00003748016	18528817	18528867
ENSE00003754081	18528559	18528682
ENSE00003891632	18530255	18530573

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 96.67.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.67	gold quality
right testis	UBERON:0004534	96.34	gold quality
testis	UBERON:0000473	95.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.29	gold quality
right frontal lobe	UBERON:0002810	78.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.22	gold quality
hypothalamus	UBERON:0001898	76.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.46	gold quality
anterior cingulate cortex	UBERON:0009835	75.67	gold quality
superior frontal gyrus	UBERON:0002661	75.36	gold quality
primary visual cortex	UBERON:0002436	74.81	gold quality
cerebral cortex	UBERON:0000956	74.42	gold quality
Ammon’s horn	UBERON:0001954	74.40	gold quality
nucleus accumbens	UBERON:0001882	73.96	gold quality
substantia nigra	UBERON:0002038	73.88	gold quality
frontal cortex	UBERON:0001870	73.79	gold quality
lower esophagus mucosa	UBERON:0035834	73.48	gold quality
temporal lobe	UBERON:0001871	73.44	gold quality
amygdala	UBERON:0001876	73.26	gold quality
granulocyte	CL:0000094	72.91	gold quality
brain	UBERON:0000955	72.70	gold quality
pituitary gland	UBERON:0000007	72.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.37	gold quality
mucosa of transverse colon	UBERON:0004991	72.22	gold quality
putamen	UBERON:0001874	71.84	gold quality
adenohypophysis	UBERON:0002196	71.40	gold quality
caudate nucleus	UBERON:0001873	71.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.63	gold quality
prefrontal cortex	UBERON:0000451	70.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting TMEM191B, 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-767-5P	99.95	70.85	993
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-6866-3P	97.38	66.94	748

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.0% of screened cell lines.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem191	ENSMUSG00000055692
rattus_norvegicus	Tmem191c	ENSRNOG00000001864

Paralogs (1): TMEM191C (ENSG00000206140)

Protein

Protein identifiers

Transmembrane protein 191B — P0C7N4 (reviewed: P0C7N4)

All UniProt accessions (2): P0C7N4, A0A087X073

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TMEM191 family.

RefSeq proteins (1): NP_001229242* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028186	TMEM191B/C	Family

Pfam: PF15194

UniProt features (4 total): chain 1, transmembrane region 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C7N4-F1	74.28	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): PAF1_TARGET_GENES, ZNF282_TARGET_GENES, ZSCAN21_TARGET_GENES, MIR3664_3P, MIR4780, ZBTB5_TARGET_GENES, ZNF394_TARGET_GENES, CC2D1A_TARGET_GENES, ZNF579_TARGET_GENES, HE_LIM_SUN_FETAL_LUNG_C0_LATE_MESOTHELIAL_CELL, HE_LIM_SUN_FETAL_LUNG_C2_DC1_CELL, chr22q11

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM191B	RIMBP3B	A6NNM3	620
TMEM191B	RIMBP3	Q9UFD9	583
TMEM191B	FAM47B	Q8NA70	576
TMEM191B	OR13C8	Q8NGS7	544
TMEM191B	LRRC14B	A6NHZ5	505
TMEM191B	DGCR6	Q14129	476
TMEM191B	TMEM236	Q5W0B7	476
TMEM191B	TTC9	Q92623	445
TMEM191B	PRODH	O43272	439
TMEM191B	DGCR6L	Q9BY27	425
TMEM191B	GGT2P	P36268	404
TMEM191B	PRODH	O43272	401
TMEM191B	DCAF5	Q96JK2	400
TMEM191B	TSSK2	Q96PF2	398
TMEM191B	OTOGL	Q3ZCN5	376

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0JNH6, A1A5D9, A6NC98, A6NGB0, A6NJZ7, A6NNM3, F6XLV1, O15049, O54887, P0C7N4, P58660, P60531, Q0D2H9, Q0P5D1, Q2KJ21, Q2TAC2, Q3LUD3, Q3T1I3, Q3TMW1, Q3V0F0, Q4QRL3, Q5JTB6, Q5RD60, Q66HR5, Q6NSJ2, Q6PHN1, Q6QZQ4, Q80VM7, Q8BP01, Q8C7U1, Q8CB62, Q8CGU1, Q8CHW5, Q8K2I2, Q8N137, Q8N283, Q8N6Y0, Q8R370

Diamond homologs: A6NGB0, P0C7N4, Q9JJB1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1703639	GRCh37/hg19 22q11.21(chr22:18645353-21800797)	Pathogenic
625679	GRCh37/hg19 22q11.21(chr22:18892575-21460220)	Pathogenic

SpliceAI

1204 predictions. Top by Δscore:

Variant	Effect	Δscore
22:18528254:GACC:G	donor_gain	1.0000
22:18528674:G:GT	donor_gain	1.0000
22:18528683:G:GG	donor_gain	1.0000
22:18528684:T:A	donor_loss	1.0000
22:18528688:G:GT	donor_gain	1.0000
22:18529439:A:G	acceptor_gain	1.0000
22:18529604:A:AG	acceptor_gain	1.0000
22:18529605:G:GG	acceptor_gain	1.0000
22:18529605:GGAC:G	acceptor_gain	1.0000
22:18529857:G:GG	donor_gain	1.0000
22:18529862:G:GT	donor_gain	1.0000
22:18529863:G:T	donor_gain	1.0000
22:18530007:GA:G	donor_gain	1.0000
22:18530009:G:GG	donor_gain	1.0000
22:18530309:G:A	acceptor_gain	1.0000
22:18528274:G:GT	donor_gain	0.9900
22:18528677:GAC:G	donor_gain	0.9900
22:18529438:A:AG	acceptor_gain	0.9900
22:18529494:GCAG:G	donor_gain	0.9900
22:18529497:GG:G	donor_loss	0.9900
22:18529498:GT:G	donor_loss	0.9900
22:18529600:A:AG	acceptor_gain	0.9900
22:18529601:C:G	acceptor_gain	0.9900
22:18529601:CCCA:C	acceptor_loss	0.9900
22:18529603:CAG:C	acceptor_loss	0.9900
22:18529604:AG:A	acceptor_gain	0.9900
22:18529605:G:GC	acceptor_loss	0.9900
22:18529605:GG:G	acceptor_gain	0.9900
22:18529605:GGA:G	acceptor_gain	0.9900
22:18529720:GGGCG:G	donor_gain	0.9900

AlphaMissense

2173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:18529022:T:C	F159L	0.985
22:18529024:C:A	F159L	0.985
22:18529024:C:G	F159L	0.985
22:18528195:T:C	L72P	0.980
22:18528160:G:C	K60N	0.979
22:18528160:G:T	K60N	0.979
22:18528153:T:C	L58S	0.976
22:18528161:G:C	D61H	0.973
22:18529639:T:C	F213L	0.972
22:18529641:C:A	F213L	0.972
22:18529641:C:G	F213L	0.972
22:18528183:G:C	R68P	0.971
22:18528204:T:C	L75P	0.969
22:18528162:A:T	D61V	0.967
22:18528173:G:C	G65R	0.966
22:18528177:G:C	R66P	0.963
22:18528862:A:C	S156R	0.963
22:18528864:T:A	S156R	0.963
22:18528864:T:G	S156R	0.963
22:18528168:G:C	R63P	0.960
22:18528166:C:A	N62K	0.959
22:18528166:C:G	N62K	0.959
22:18528162:A:C	D61A	0.958
22:18528174:G:A	G65D	0.958
22:18528849:G:C	W151C	0.958
22:18528849:G:T	W151C	0.958
22:18528857:T:C	L154P	0.948
22:18529984:G:A	M257I	0.947
22:18529984:G:C	M257I	0.947
22:18529984:G:T	M257I	0.947

dbSNP variants (sampled 300 via entrez): RS1000506001 (22:18527221 G>A), RS1002176803 (22:18530677 C>T), RS1002312421 (22:18530046 G>A,T), RS1005878171 (22:18528135 A>G), RS1006586266 (22:18528788 T>C,G), RS1009728177 (22:18527297 C>T), RS1010986021 (22:18530694 C>T), RS1011455518 (22:18530064 TC>T,TCC,TCCC), RS1014177464 (22:18529817 C>T), RS1015905642 (22:18528765 G>C), RS1016297535 (22:18528160 G>T), RS1017041211 (22:18531018 T>TTC), RS1019477244 (22:18527354 G>A,T), RS1019952815 (22:18526069 T>C), RS1021207115 (22:18530069 C>A,G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:188400

GenCC curated gene-disease

Mondo (1): DiGeorge syndrome (MONDO:0008564)

Orphanet (1): 22q11.2 deletion syndrome (Orphanet:567)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004062	DiGeorge Syndrome	C05.660.207.103.500; C14.240.400.021.500; C14.280.400.044.500; C15.604.451.249.500; C16.131.077.019.500; C16.131.240.400.021.500; C16.131.260.019.500; C16.131.482.249.500; C16.131.621.207.103.500; C16.320.180.019.500; C19.642.482.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
licochalcone B	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects response to substance, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Genistein	affects cotreatment, decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00395538	PHASE3	TERMINATED	Effects of PTH Replacement on Bone in Hypoparathyroidism
NCT00576407	PHASE2	COMPLETED	Thymus Transplantation in DiGeorge Syndrome #668
NCT00576836	PHASE2	COMPLETED	Thymus Transplantation Dose in DiGeorge #932
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT05149898	PHASE2	COMPLETED	Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00566488	PHASE1	COMPLETED	Parathyroid and Thymus Transplantation in DiGeorge #931
NCT00579709	PHASE1	COMPLETED	Thymus Transplantation With Immunosuppression
NCT00849888	PHASE1	TERMINATED	Serum-Free Thymus Transplantation in DiGeorge Anomaly
NCT02895906	PHASE1	COMPLETED	Safety and Efficacy Study of NFC-1 in Subjects Aged 12-17 Years With 22q11.2DS & Associated Neuropsychiatric Conditions
NCT00579527	PHASE1/PHASE2	COMPLETED	Phase I/II Thymus Transplantation With Immunosuppression #950
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT00105274	Not specified	COMPLETED	Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study
NCT00278005	Not specified	TERMINATED	Infection in DiGeorge Following CHD Surgery
NCT00556530	Not specified	RECRUITING	Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome
NCT00916955	Not specified	COMPLETED	Genetic Modifiers for 22q11.2 Syndrome
NCT01220531	Not specified	COMPLETED	Thymus Transplantation Safety-Efficacy
NCT01781923	Not specified	COMPLETED	Cognitive Remediation in 22q11DS
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02430584	Not specified	UNKNOWN	Whole Blood Specimen Collection From Pregnant Subjects
NCT02460328	Not specified	COMPLETED	Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome
NCT02787486	Not specified	COMPLETED	Expanded Noninvasive Genomic Medical Assessment: The Enigma Study
NCT03284060	Not specified	TERMINATED	Social Cognition Training and Cognitive Remediation
NCT04141540	Not specified	COMPLETED	Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11
NCT04373226	Not specified	TERMINATED	Arithmetic Abilities in Children With 22q11.2DS
NCT04639388	Not specified	RECRUITING	Understanding of Psychotic Disorders in Children With 22q11.2DS
NCT04639960	Not specified	TERMINATED	Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome
NCT04647500	Not specified	COMPLETED	Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome
NCT05924347	Not specified	RECRUITING	Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders