TMEM91

Summary

TMEM91 (transmembrane protein 91, HGNC:32393) is a protein-coding gene on chromosome 19q13.2, encoding Transmembrane protein 91 (Q6ZNR0).

Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be active in intracellular membrane-bounded organelle and membrane.

Source: NCBI Gene 641649 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_001098821

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32393
Approved symbol	TMEM91
Name	transmembrane protein 91
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ27310, IFITMD6, DSPC3, SynDIG3
Ensembl gene	ENSG00000142046
Ensembl biotype	protein_coding
OMIM	618294
Entrez	641649

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 22 protein_coding

ENST00000342187, ENST00000356385, ENST00000392002, ENST00000413014, ENST00000436170, ENST00000447302, ENST00000535712, ENST00000537354, ENST00000539627, ENST00000542945, ENST00000544232, ENST00000546050, ENST00000546362, ENST00000604123, ENST00000889861, ENST00000889862, ENST00000889863, ENST00000889864, ENST00000966284, ENST00000966285, ENST00000966286, ENST00000966287

RefSeq mRNA: 8 — MANE Select: NM_001098821 NM_001042595, NM_001098821, NM_001098822, NM_001098823, NM_001098824, NM_001098825, NM_001369862, NM_001369864

CCDS: CCDS42571, CCDS42572, CCDS46082, CCDS46083, CCDS46084

Canonical transcript exons

ENST00000392002 — 4 exons

Exon	Start	End
ENSE00001374958	41382772	41382921
ENSE00001386919	41383715	41384083
ENSE00001402202	41376533	41376854
ENSE00003692982	41378281	41378519

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 96.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6936 / max 228.2297, expressed in 1792 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176020	7.6241	1665
176023	2.4137	851
176025	1.4101	523
176013	0.5295	142
176021	0.2909	122
176018	0.2012	89
176024	0.1297	59
176012	0.0612	18
176019	0.0331	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	96.27	gold quality
upper arm skin	UBERON:0004263	95.96	gold quality
oviduct epithelium	UBERON:0004804	95.91	gold quality
monocyte	CL:0000576	95.29	gold quality
leukocyte	CL:0000738	94.93	gold quality
putamen	UBERON:0001874	94.61	gold quality
tendon of biceps brachii	UBERON:0008188	94.03	gold quality
caudate nucleus	UBERON:0001873	93.97	gold quality
granulocyte	CL:0000094	93.66	gold quality
blood	UBERON:0000178	93.55	gold quality
hypothalamus	UBERON:0001898	93.31	gold quality
skin of abdomen	UBERON:0001416	93.03	gold quality
buccal mucosa cell	CL:0002336	92.44	gold quality
right uterine tube	UBERON:0001302	92.35	gold quality
endocervix	UBERON:0000458	91.70	gold quality
ectocervix	UBERON:0012249	90.61	gold quality
left testis	UBERON:0004533	90.55	gold quality
nipple	UBERON:0002030	90.34	gold quality
right lung	UBERON:0002167	90.31	gold quality
zone of skin	UBERON:0000014	90.11	gold quality
right testis	UBERON:0004534	90.10	gold quality
skin of leg	UBERON:0001511	90.09	gold quality
lower esophagus mucosa	UBERON:0035834	90.04	gold quality
vagina	UBERON:0000996	89.94	gold quality
uterine cervix	UBERON:0000002	89.63	gold quality
mammalian vulva	UBERON:0000997	89.54	gold quality
mucosa of stomach	UBERON:0001199	89.39	gold quality
pericardium	UBERON:0002407	89.37	gold quality
amygdala	UBERON:0001876	89.30	gold quality
spleen	UBERON:0002106	89.28	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.48
E-MTAB-6058	no	30.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting TMEM91, 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-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-647	97.73	67.79	927
HSA-MIR-4632-3P	96.26	58.52	123

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem91	ENSDARG00000068456
mus_musculus	Tmem91	ENSMUSG00000061702
rattus_norvegicus	Tmem91	ENSRNOG00000068180

Paralogs (3): SYNDIG1 (ENSG00000101463), SYNDIG1L (ENSG00000183379), PMIS2 (ENSG00000283758)

Protein

Protein identifiers

Transmembrane protein 91 — Q6ZNR0 (reviewed: Q6ZNR0)

Alternative names: Dispanin subfamily C member 3

All UniProt accessions (8): Q6ZNR0, F5GWC9, F5H665, F8W6Q6, H0YFW9, H0YG43, H0YGI4, S4R3Y8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the CD225/Dispanin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6ZNR0-1	1	yes
Q6ZNR0-2	2
Q6ZNR0-3	3
Q6ZNR0-4	4
Q6ZNR0-5	5

RefSeq proteins (8): NP_001036060, NP_001092291, NP_001092292, NP_001092293, NP_001092294, NP_001092295, NP_001356791, NP_001356793 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007593	CD225/Dispanin_fam	Family

Pfam: PF04505

UniProt features (15 total): splice variant 4, topological domain 3, sequence conflict 2, transmembrane region 2, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZNR0-F1	58.55	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, ATF6_TARGET_GENES, GLI3_TARGET_GENES, HES2_TARGET_GENES, HOXC6_TARGET_GENES, IRF5_TARGET_GENES, NAB2_TARGET_GENES, SKIL_TARGET_GENES, SUPT16H_TARGET_GENES, UBN1_TARGET_GENES, ZBTB18_TARGET_GENES

GO Biological Process (2): hematopoietic progenitor cell differentiation (GO:0002244), biological_process (GO:0008150)

GO Molecular Function (2): molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (2): membrane (GO:0016020), cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hemopoiesis	1
cell differentiation	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM91	TMEM233	B4DJY2	635
TMEM91	GSG1L2	A8MUP6	617
TMEM91	PRRT1B	A0A1B0GWB2	554
TMEM91	ANKRD13B	Q86YJ7	534
TMEM91	TMEM25	Q86YD3	529
TMEM91	B9D2	Q9BPU9	523
TMEM91	TRARG1	Q8IXB3	509
TMEM91	RTN4RL2	Q86UN3	460
TMEM91	SEZ6L2	Q6UXD5	456
TMEM91	EML1	O00423	453
TMEM91	PIP5KL1	Q5T9C9	451
TMEM91	PLPPR3	Q6T4P5	424
TMEM91	TMEM278	A6NKF7	422
TMEM91	TMEM145	Q8NBT3	421
TMEM91	PAK6	Q9NQU5	414

IntAct

1 interactions, top by confidence:

BioGRID (2): TMEM91 (Affinity Capture-RNA), TMEM91 (Two-hybrid)

ESM2 similar proteins: A0A0U1RQ45, A0A1B0GWB2, A2A9T0, A6QPA0, A7MCY6, D3ZFB6, E9PUL5, E9Q0B3, F5GYI3, F5H4A9, J3QNX5, O70142, P0C1G7, P81408, P97764, P98077, Q148V8, Q15654, Q2KI80, Q3SX26, Q3SZL6, Q4V9L6, Q5FVJ4, Q5FW56, Q5RAC1, Q5T7N3, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZNR0, Q6ZRV2, Q75VX8, Q7Z6L0, Q86UK7, Q86VE0, Q8BGW2, Q8BRJ3, Q8BX43, Q8C0R7

Diamond homologs: A2ANU3, A4IFJ1, A6NDD5, O35449, Q08DM6, Q3USQ7, Q4R532, Q58DZ9, Q5TZE2, Q6MG82, Q6ZNR0, Q8C581, Q99946, Q9H7V2, A0A1B0GWB2, B4DJY2, D3Z1U7, D3ZFB6, E9PUL5, Q2MHH0, Q5RAC1, Q6DFT4, Q7Z6L0, Q8C838, Q8IXB3, Q91499

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1715 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41352725:T:TA	donor_gain	1.0000
19:41357892:CCCA:C	donor_loss	1.0000
19:41357893:CCA:C	donor_loss	1.0000
19:41357894:CA:C	donor_loss	1.0000
19:41357895:ACCTT:A	donor_loss	1.0000
19:41357896:C:A	donor_loss	1.0000
19:41361128:G:C	donor_gain	1.0000
19:41363971:A:C	donor_gain	1.0000
19:41352687:CAC:C	donor_loss	0.9900
19:41357899:TGAAG:T	donor_gain	0.9900
19:41363467:T:A	donor_gain	0.9900
19:41363956:AC:A	donor_loss	0.9900
19:41363957:CCTT:C	donor_loss	0.9900
19:41363970:A:AC	donor_gain	0.9900
19:41364111:T:TA	donor_gain	0.9900
19:41376829:G:GT	donor_gain	0.9900
19:41376850:GAGCG:G	donor_gain	0.9900
19:41376852:GCG:G	donor_gain	0.9900
19:41376853:CGGTG:C	donor_loss	0.9900
19:41376854:GGTG:G	donor_loss	0.9900
19:41376855:G:GG	donor_gain	0.9900
19:41376855:GTGA:G	donor_loss	0.9900
19:41376857:GAGT:G	donor_loss	0.9900
19:41376858:AGTG:A	donor_loss	0.9900
19:41376865:G:T	donor_gain	0.9900
19:41378275:CCCTA:C	acceptor_loss	0.9900
19:41378276:CCTA:C	acceptor_loss	0.9900
19:41378276:CCTAG:C	acceptor_loss	0.9900
19:41378277:CTA:C	acceptor_loss	0.9900
19:41378277:CTAGG:C	acceptor_loss	0.9900

AlphaMissense

1094 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41382883:T:A	W108R	0.992
19:41382883:T:C	W108R	0.992
19:41382874:T:C	C105R	0.988
19:41382877:T:C	C106R	0.987
19:41383806:G:A	G151D	0.985
19:41382892:G:C	G111R	0.983
19:41383805:G:C	G151R	0.982
19:41382893:G:A	G111D	0.981
19:41383811:T:C	C153R	0.981
19:41382902:C:A	A114D	0.979
19:41382887:C:A	P109H	0.978
19:41382880:T:C	F107L	0.977
19:41382882:C:A	F107L	0.977
19:41382882:C:G	F107L	0.977
19:41382904:T:C	F115L	0.977
19:41382906:C:A	F115L	0.977
19:41382906:C:G	F115L	0.977
19:41383784:G:A	G144R	0.977
19:41383784:G:C	G144R	0.977
19:41383794:C:A	A147D	0.977
19:41382887:C:G	P109R	0.976
19:41382890:T:A	V110D	0.976
19:41382857:C:A	A99D	0.975
19:41382899:C:A	A113D	0.974
19:41382860:T:A	V100D	0.972
19:41382878:G:A	C106Y	0.967
19:41383799:G:A	G149R	0.965
19:41383799:G:C	G149R	0.965
19:41382869:T:A	M103K	0.964
19:41382896:T:A	I112N	0.964

dbSNP variants (sampled 300 via entrez): RS1000035995 (19:41374661 C>G), RS1000059320 (19:41384096 C>A,T), RS1000106271 (19:41373382 A>G), RS1000751328 (19:41363917 C>A,G,T), RS1000859501 (19:41371074 T>G), RS1000896406 (19:41370892 A>G,T), RS1000969682 (19:41377465 G>A), RS1001044338 (19:41365110 T>A), RS1001567130 (19:41373648 C>T), RS1001711421 (19:41367942 G>A), RS1001867915 (19:41372561 T>C), RS1002170906 (19:41375031 C>A,T), RS1002187622 (19:41366083 C>A,T), RS1002223485 (19:41375276 T>TTC), RS1002262750 (19:41362078 C>A)

Disease associations

OMIM: gene MIM:618294 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004898_3	Preterm birth (maternal effect)	5.000000e-07
GCST006988_121	Blond vs. brown/black hair color	8.000000e-12
GCST010479_46	Coronary artery disease	4.000000e-11
GCST010867_22	Coronary artery disease	8.000000e-15
GCST90002385_513	High light scatter reticulocyte count	2.000000e-11
GCST90002386_208	High light scatter reticulocyte percentage of red cells	5.000000e-12
GCST90002405_550	Reticulocyte count	3.000000e-12
GCST90002406_530	Reticulocyte fraction of red cells	4.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003917	premature birth
EFO:0005939	parental genotype effect measurement
EFO:0003924	hair color
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800469	B9D2, TGFB1, TMEM91	3	2.50	2	aspirin;irinotecan
rs1800470	TGFB1, TMEM91	3	2.75	1	rituximab
rs1800471	TGFB1, TMEM91	3	3.25	1	rituximab
rs75041078	TMEM91	3	0.00	1	glatiramer acetate

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression, increases methylation	1
ethylene dichloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Pioglitazone	increases expression	1
Decitabine	affects expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1
Cisplatin	affects expression	1
Diuron	decreases expression	1
Estradiol	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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