TMIGD1

Summary

TMIGD1 (transmembrane and immunoglobulin domain containing 1, HGNC:32431) is a protein-coding gene on chromosome 17q11.2, encoding Transmembrane and immunoglobulin domain-containing protein 1 (Q6UXZ0). May control cell-cell adhesion, cell migration and proliferation, cell morphology, and protects renal epithelial cells from oxidative cell injury to promote cell survival.

Predicted to enable cell-cell adhesion mediator activity and protein homodimerization activity. Involved in several processes, including negative regulation of apoptotic process; regulation of cell migration; and regulation of membrane permeability. Located in cytosol; mitochondrion; and plasma membrane.

Source: NCBI Gene 388364 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_206832

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32431
Approved symbol	TMIGD1
Name	transmembrane and immunoglobulin domain containing 1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	UNQ9372
Ensembl gene	ENSG00000182271
Ensembl biotype	protein_coding
OMIM	621206
Entrez	388364

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000328886, ENST00000538566, ENST00000854986, ENST00000956357

RefSeq mRNA: 2 — MANE Select: NM_206832 NM_001319942, NM_206832

CCDS: CCDS32605, CCDS82099

Canonical transcript exons

ENST00000328886 — 7 exons

Exon	Start	End
ENSE00001290474	30329251	30329529
ENSE00001299265	30318810	30318913
ENSE00001309833	30324816	30325094
ENSE00001369097	30334000	30334057
ENSE00001389548	30316333	30316690
ENSE00001710969	30332052	30332158
ENSE00003623264	30317193	30317233

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 97.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0619 / max 51.2410, expressed in 8 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165188	0.0619	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	97.63	gold quality
mucosa of transverse colon	UBERON:0004991	96.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.79	gold quality
transverse colon	UBERON:0001157	83.43	gold quality
small intestine	UBERON:0002108	82.96	gold quality
intestine	UBERON:0000160	69.86	gold quality
colon	UBERON:0001155	64.81	gold quality
colonic epithelium	UBERON:0000397	59.38	gold quality
adult mammalian kidney	UBERON:0000082	56.97	gold quality
smooth muscle tissue	UBERON:0001135	53.16	gold quality
kidney	UBERON:0002113	51.76	gold quality
duodenum	UBERON:0002114	51.48	gold quality
vermiform appendix	UBERON:0001154	47.84	gold quality
cortex of kidney	UBERON:0001225	43.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	42.83	gold quality
metanephros cortex	UBERON:0010533	39.77	gold quality
muscle tissue	UBERON:0002385	38.74	gold quality
sural nerve	UBERON:0015488	37.07	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
mucosa of stomach	UBERON:0001199	36.09	silver quality
right coronary artery	UBERON:0001625	35.49	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.97	gold quality
monocyte	CL:0000576	33.65	gold quality
leukocyte	CL:0000738	33.10	gold quality
lymph node	UBERON:0000029	32.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting TMIGD1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-500A-3P	97.60	67.48	595
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-4540	96.90	67.46	473

Literature-anchored findings (GeneRIF, showing 5)

• identified TMIGD1 as a novel cell adhesion molecule expressed in kidney epithelial cells that protects kidney epithelial cells from oxidative cell injury to promote cell survival (PMID:26342724)
• The mitochondrial outer membrane protein SYNJ2BP interacts with the cell adhesion molecule TMIGD1 and can recruit it to mitochondria. (PMID:32303178)
• Transcriptomic identification of TMIGD1 and its relationship with the ileal epithelial cell differentiation in Crohn’s disease. (PMID:32508154)
• Transmembrane and Immunoglobulin Domain Containing 1, a Putative Tumor Suppressor, Induces G2/M Cell Cycle Checkpoint Arrest in Colon Cancer Cells. (PMID:33129760)
• The Role of TMIGD1 as a Tumor Suppressor in Colorectal Cancer. (PMID:35481970)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmigd1	ENSDARG00000007040
mus_musculus	Tmigd1	ENSMUSG00000020839
rattus_norvegicus	Tmigd1	ENSRNOG00000003865

Protein

Protein identifiers

Transmembrane and immunoglobulin domain-containing protein 1 — Q6UXZ0 (reviewed: Q6UXZ0)

All UniProt accessions (1): Q6UXZ0

UniProt curated annotations — full annotation on UniProt →

Function. May control cell-cell adhesion, cell migration and proliferation, cell morphology, and protects renal epithelial cells from oxidative cell injury to promote cell survival.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane. Cytoplasm.

Post-translational modifications. N-glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UXZ0-1	1	yes
Q6UXZ0-2	2

RefSeq proteins (2): NP_001306871, NP_996663* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051275	Cell_adhesion_signaling	Family

Pfam: PF00047, PF07679

UniProt features (16 total): glycosylation site 5, disulfide bond 2, splice variant 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8CD3	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXZ0-F1	87.67	0.69

Functional residue map

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

Disulfide bonds (2): 54–103, 143–195

Glycosylation sites (5): 158, 190, 58, 83, 118

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, LHX3_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr17q11, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_CELL_CELL_ADHESION, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_TISSUE_MIGRATION

GO Biological Process (15): response to nutrient (GO:0007584), intracellular protein localization (GO:0008104), regulation of cell migration (GO:0030334), regulation of cell population proliferation (GO:0042127), negative regulation of apoptotic process (GO:0043066), cell-cell junction organization (GO:0045216), negative regulation of epithelial cell proliferation (GO:0050680), intestinal epithelial cell maturation (GO:0060574), intestinal epithelial cell migration (GO:0061582), cellular response to hydroperoxide (GO:0071447), regulation of membrane permeability (GO:0090559), cell aggregation (GO:0098743), brush border assembly (GO:1904970), cell migration (GO:0016477), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): protein homodimerization activity (GO:0042803), cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515), cell adhesion mediator activity (GO:0098631)

GO Cellular Component (8): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), cell surface (GO:0009986), neuron projection (GO:0043005), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell adhesion	2
cytoplasm	2
response to nutrient levels	1
response to chemical	1
macromolecule localization	1
cell migration	1
regulation of cell motility	1
cell population proliferation	1
regulation of cellular process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell junction organization	1
negative regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
columnar/cuboidal epithelial cell maturation	1
intestinal epithelial cell development	1
epithelial cell migration	1
response to hydroperoxide	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
regulation of biological quality	1
cellular process	1
cellular component assembly	1
cell motility	1
identical protein binding	1
protein dimerization activity	1
cell-cell adhesion	1
cell adhesion mediator activity	1
binding	1
cell adhesion molecule binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cell-cell junction	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMIGD1	SYNJ2BP	P57105	623
TMIGD1	CLRN3	Q8NCR9	623
TMIGD1	MS4A12	Q9NXJ0	601
TMIGD1	TMIGD3	P0DMS9	583
TMIGD1	SLC10A2	Q12908	544
TMIGD1	SLC6A19	Q695T7	500
TMIGD1	ZG16	O60844	479
TMIGD1	MRM3	Q9HC36	455
TMIGD1	CLCA4	Q14CN2	448
TMIGD1	GUCA2B	Q16661	440
TMIGD1	OTOP2	Q7RTS6	436
TMIGD1	SLC5A1	P13866	434
TMIGD1	GUCA2A	Q02747	434
TMIGD1	TMIGD2	Q96BF3	424
TMIGD1	BEST4	Q8NFU0	417

IntAct

132 interactions, top by confidence:

A	B	Type	Score
SCRIB	TMIGD1	psi-mi:“MI:0915”(physical association)	0.710
TMIGD1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.710
BANF1	TMIGD1	psi-mi:“MI:0915”(physical association)	0.640
BANF1	TMIGD1	psi-mi:“MI:0407”(direct interaction)	0.640
BANF1	TMIGD1	psi-mi:“MI:0403”(colocalization)	0.640
TMIGD1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.610
TMIGD1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.610
SNX27	TMIGD1	psi-mi:“MI:0915”(physical association)	0.610
MAST2	TMIGD1	psi-mi:“MI:0915”(physical association)	0.610
TMIGD1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
SYNJ2BP	TMIGD1	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
TMIGD1	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1): TMIGD1 (Proximity Label-MS)

ESM2 similar proteins: A6QQC6, A8MVW5, B0CLX4, O02671, O18906, O88324, O88775, O95976, P00545, P01881, P01882, P03228, P08920, P08921, P0C6B7, P0C6N0, P0CW72, P0DUB1, P20746, P21995, P35329, P42071, P42082, P48356, P48357, P86176, P97378, Q01151, Q3T113, Q3U0X8, Q4VAH7, Q5BK49, Q62959, Q6GMZ9, Q6PCB8, Q6UXZ0, Q80UL9, Q8CFD9, Q8IW00, Q8K4F0

Diamond homologs: A0JM20, A0N0X6, A1KZ92, A2ABU4, A2CG49, A3KN33, A4IGL7, B4F785, D2HFT7, D3YXG0, D3ZEY0, E9Q8Q6, G5EBF1, G5EEY6, O02827, O15146, O55005, O60229, O88792, O89026, P0C6S8, P17948, P29294, P35969, P53767, P54296, P56276, P57087, P70193, P97924, Q01974, Q08E66, Q14896, Q1RMS4, Q32Q07, Q3UQ28, Q3URE9, Q4VBE4, Q52KR2, Q5MD89

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	53.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	51.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	51.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	47.9×	6e-13
Dopamine Neurotransmitter Release Cycle	5	46.8×	2e-06
Long-term potentiation	5	44.9×	2e-06
Neurexins and neuroligins	11	40.9×	3e-13
Protein-protein interactions at synapses	7	35.1×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	67.0×	3e-12
protein localization to synapse	6	58.9×	1e-07
receptor clustering	7	56.0×	7e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	38.1×	1e-06
cell-cell adhesion	9	11.7×	5e-06
protein-containing complex assembly	8	11.7×	2e-05
regulation of small GTPase mediated signal transduction	5	9.2×	4e-03
chemical synaptic transmission	7	6.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1171 predictions. Top by Δscore:

Variant	Effect	Δscore
17:30333996:TTA:T	donor_loss	1.0000
17:30323394:T:TA	donor_gain	0.9900
17:30329353:CAGAG:C	donor_gain	0.9900
17:30329397:C:A	donor_gain	0.9900
17:30329424:T:TA	donor_gain	0.9900
17:30333995:CTTA:C	donor_loss	0.9900
17:30333998:A:AC	donor_gain	0.9900
17:30333999:C:CC	donor_gain	0.9900
17:30333999:CCT:C	donor_gain	0.9900
17:30326687:T:TA	donor_gain	0.9800
17:30329395:T:A	donor_gain	0.9800
17:30324810:CATTA:C	donor_loss	0.9700
17:30324811:ATTAC:A	donor_loss	0.9700
17:30324812:TTACC:T	donor_loss	0.9700
17:30324813:TA:T	donor_loss	0.9700
17:30324814:A:AT	donor_loss	0.9700
17:30324815:C:CA	donor_loss	0.9700
17:30329266:C:CT	donor_gain	0.9700
17:30329357:G:C	donor_gain	0.9700
17:30332156:CTA:C	acceptor_gain	0.9700
17:30323394:TCCTC:T	donor_gain	0.9600
17:30329400:T:TA	donor_gain	0.9600
17:30333992:CCA:C	donor_gain	0.9600
17:30333998:ACCT:A	donor_gain	0.9600
17:30333999:CCTC:C	donor_gain	0.9600
17:30317192:CAGAG:C	donor_gain	0.9500
17:30325310:C:CT	acceptor_gain	0.9500
17:30329288:ATC:A	donor_gain	0.9500
17:30329318:T:TA	donor_gain	0.9500
17:30329249:A:AC	donor_gain	0.9400

AlphaMissense

1739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:30324917:A:G	L180P	0.999
17:30324991:C:A	W155C	0.999
17:30324991:C:G	W155C	0.999
17:30324993:A:G	W155R	0.999
17:30324993:A:T	W155R	0.999
17:30329411:C:A	W67C	0.999
17:30329411:C:G	W67C	0.999
17:30324827:A:G	L210P	0.998
17:30324879:A:C	Y193D	0.997
17:30324992:C:G	W155S	0.997
17:30329413:A:G	W67R	0.997
17:30329413:A:T	W67R	0.997
17:30324821:A:T	V212D	0.996
17:30329303:G:C	C103W	0.996
17:30329305:A:G	C103R	0.996
17:30329310:A:G	F101S	0.996
17:30324890:T:A	D189V	0.995
17:30325029:A:G	C143R	0.995
17:30329262:A:G	L117P	0.995
17:30329457:A:G	L52P	0.995
17:30324871:A:C	C195W	0.994
17:30324873:A:G	C195R	0.994
17:30324878:T:C	Y193C	0.994
17:30324878:T:G	Y193S	0.994
17:30329310:A:C	F101C	0.994
17:30324872:C:G	C195S	0.993
17:30324873:A:T	C195S	0.993
17:30325034:A:G	L141S	0.993
17:30329304:C:G	C103S	0.993
17:30329305:A:T	C103S	0.993

dbSNP variants (sampled 300 via entrez): RS1000057764 (17:30317453 A>G), RS1000108243 (17:30317708 TGAG>T), RS1000297573 (17:30324333 G>A), RS1000595539 (17:30335073 C>T), RS1000615328 (17:30322452 A>C,G), RS1000688903 (17:30334493 A>G), RS1000801736 (17:30328822 G>A,T), RS1000904291 (17:30322779 C>A,T), RS1001011007 (17:30315844 G>A), RS1001062155 (17:30315835 G>A), RS1001127816 (17:30317992 C>A,T), RS1001141899 (17:30334696 A>C,T), RS1001209345 (17:30322607 C>A), RS1001647118 (17:30329122 G>A,C), RS1001773075 (17:30335433 C>T)

Disease associations

OMIM: gene MIM:621206 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010241_27	Apolipoprotein A1 levels	3.000000e-17
GCST90000025_579	Appendicular lean mass	2.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-palmitoylglycerol	increases expression	1
Aflatoxin B1	decreases methylation	1
Palmitic Acid	decreases expression	1

Clinical trials (associated diseases)

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