TIMD4

Summary

TIMD4 (T cell immunoglobulin and mucin domain containing 4, HGNC:25132) is a protein-coding gene on chromosome 5q33.3, encoding T-cell immunoglobulin and mucin domain-containing protein 4 (Q96H15). Phosphatidylserine receptor that plays different role in immune response including phagocytosis of apoptotic cells and T-cell regulation.

Predicted to enable phosphatidylserine binding activity. Predicted to be involved in apoptotic cell clearance and cytoskeletal rearrangement involved in phagocytosis, engulfment. Predicted to be located in extracellular region and plasma membrane.

Source: NCBI Gene 91937 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 58 total — 1 pathogenic
• MANE Select transcript: NM_138379

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25132
Approved symbol	TIMD4
Name	T cell immunoglobulin and mucin domain containing 4
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Aliases	TIM4
Ensembl gene	ENSG00000145850
Ensembl biotype	protein_coding
OMIM	610096
Entrez	91937

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000274532, ENST00000406964, ENST00000407087

RefSeq mRNA: 2 — MANE Select: NM_138379 NM_001146726, NM_138379

CCDS: CCDS4332, CCDS54943

Canonical transcript exons

ENST00000274532 — 9 exons

Exon	Start	End
ENSE00001023147	156954415	156954756
ENSE00001023148	156951512	156951790
ENSE00001023149	156949651	156949731
ENSE00001023150	156920464	156920503
ENSE00001023151	156963141	156963226
ENSE00001023154	156948416	156948499
ENSE00001903663	156919292	156919541
ENSE00003549096	156926263	156926312
ENSE00003758887	156922099	156922216

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 97.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8067 / max 221.2826, expressed in 66 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64484	0.6769	62
64481	0.0882	5
64482	0.0297	3
64483	0.0119	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.51	gold quality
right testis	UBERON:0004534	97.25	gold quality
testis	UBERON:0000473	93.54	gold quality
sperm	CL:0000019	93.20	silver quality
lymph node	UBERON:0000029	91.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.71	gold quality
oocyte	CL:0000023	87.57	gold quality
trabecular bone tissue	UBERON:0002483	84.45	gold quality
synovial joint	UBERON:0002217	81.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.10	gold quality
superficial temporal artery	UBERON:0001614	78.84	gold quality
spleen	UBERON:0002106	77.59	gold quality
adult organism	UBERON:0007023	76.83	silver quality
vermiform appendix	UBERON:0001154	76.45	gold quality
secondary oocyte	CL:0000655	72.60	silver quality
layer of synovial tissue	UBERON:0007616	71.88	gold quality
germinal epithelium of ovary	UBERON:0001304	70.36	gold quality
liver	UBERON:0002107	69.17	gold quality
caecum	UBERON:0001153	68.68	gold quality
metanephros cortex	UBERON:0010533	68.28	gold quality
bone marrow cell	CL:0002092	67.02	gold quality
bone marrow	UBERON:0002371	67.02	gold quality
adult mammalian kidney	UBERON:0000082	65.83	gold quality
mucosa of transverse colon	UBERON:0004991	65.37	gold quality
cortex of kidney	UBERON:0001225	65.23	gold quality
right lobe of liver	UBERON:0001114	65.06	gold quality
granulocyte	CL:0000094	64.66	gold quality
gall bladder	UBERON:0002110	62.33	gold quality
thymus	UBERON:0002370	60.22	gold quality
metanephros	UBERON:0000081	60.03	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	1191.16
E-HCAD-4	yes	331.34
E-ANND-3	no	3.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting TIMD4, 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-8087	99.90	69.55	1351
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-924	97.78	66.21	681
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048

Literature-anchored findings (GeneRIF, showing 40)

• The polymorphism of 8570G > A in TIM4 may be associated with allergic asthma in the population of Han nationality from Hubei province of China. (PMID:17407086)
• The results demonstrate that Staphylococcus aureus derived Staphylococcal enterotoxin B promotes the TIM4 production in human dendritic cells. (PMID:17439824)
• TIM-4 and TIM-1 are immunologically restricted members of the group of receptors whose recognition of PS is critical for the efficient clearance of apoptotic cells and prevention of autoimmunity. (PMID:18082433)
• Structures of T cell immunoglobulin mucin protein 4 show a metal-Ion-dependent ligand binding site where phosphatidylserine binds. (PMID:18083575)
• There were four SNPs in the promoter region of TIM4 in asthma patients of Chinese Han population, which were in linkage disequilibrium. (PMID:18704309)
• Data show that the transmembrane region and cytoplasmic tail of TIM-4 are dispensable for apoptotic cell engulfment, and suggest that TIM-4 is a PtdSer tethering receptor without any direct signaling of its own. (PMID:19217291)
• TIM4 -1419G>A polymorphism might be the genetic factor for the risk of childhood asthma in Chinese Han population. (PMID:19392790)
• results showed that Tim-4 mRNA expression in peripheral blood mononuclear cells was significantly higher in system lupus erythematosus patients than in healthy controls, especially those patients in the active phase of disease. (PMID:20140011)
• Histiocytic and dendritic cell neoplasms consistently express TIM-3 and TIM-4 and that these molecules are new markers of neoplasms derived from histiocytic and dendritic cells. (PMID:20656318)
• TIM-4 gene polymorphisms are associated with asthma in a Chinese Han population. (PMID:20727045)
• Overexpression of TIM-4 on antigen- presenting cells in transgenic mice reduces the number of antigen-specific T cells that remain after immunization, resulting in reduced secondary T cell responses. (PMID:21037090)
• macrophage-derived TIM4 plays an important role in the induction of Tregs in gliomas, which may play an important role in tumor tolerance. (PMID:21896488)
• TIM-4 variant or a highly correlated nearby gene of the TIM-4 gene may play a critical role in the pathogenesis of rheumatoid arthritis in many ethnicities. (PMID:22353209)
• FG-CC’ siRNA blocking interaction of Tim-1 and Tim-4 can enhance dendritic cell vaccine activity against gastric cancer. (PMID:22709877)
• TIM4 expression is promoted by Cockroach allergen Bla g 7 in dendritic cells leading to Th2 polarization (PMID:24204099)
• Our results do not support an association between the rs7700944 polymorphism of the TIM-4 gene and rheumatoid arthritis (PMID:24217665)
• TIM-1 and TIM-4 are novel targets for ADAM10- and ADAM17-mediated ectodomain shedding. (PMID:24286866)
• Data suggest that genetic polymorphisms in ANGPTL3 (angiopoietin-like 3 protein), TIMD4 (T cell immunoglobulin mucin-4), and apolipoproteins A5 and B are among the genetic determinants of hypertriglyceridemia in Amerindian populations. [REVIEW] (PMID:24768220)
• Our study uncovers a novel ability of TIM-family proteins to block the release of HIV-1 and other viruses by interaction with virion- and cell-associated phosphatidylserine. (PMID:25136083)
• Tim-4 expression on monocytes and Tim-4 level in plasma were more highly increased in ankylosing spondylitis patients than in controls. (PMID:25359708)
• Data indicate that T cell immunoglobulin and mucin domain containing 4 (TIM-4) contributes, at least in part, to the pathogenesis of type 2 diabetes mellitus (T2D), possibly by regulating interleukin-1beta (IL-1beta). (PMID:25676395)
• TIM-4 rs7700944 and not TIM-1 rs41297579 G>A (-1454) is associated with rheumatoid arthritis(RA) in the present cohort of Egyptian and may be a risk factor for development of RA in Egyptian. (PMID:25899833)
• TIM4 binds TIM3 on the surface of polarized Th1 cells to induce Th1 cell apoptosis, which may contribute to the development of Th2-dominant immune disorders. (PMID:26403707)
• Data showed up-regulation of TIM-4 in lung cancer tissues and a correlation with poor prognosis. Also, TIM-4 was found to promote growth of lung cancer cells by its interaction with integrin alphavbeta3 through its RGD motif. (PMID:26512878)
• Tim-4 expression is closely associated with glioma and may have a regulatory role (PMID:26741116)
• analysis of the molecular characteristics of both mTIM-4 and hTIM-4 provides a better understanding of the regions of the TIM-4 IgV domain critical for Ebola virus entry (PMID:27122575)
• VitD deficiency may contribute to the pathogenesis of allergic rhinitis (AR) by increasing the TIM4 expression. The results suggest that to regulate the serum calcitriol levels and the expression of VDR in DCs may be necessary to be taken into account in the treatment of AR. (PMID:28160341)
• This study aimed to investigate the association of two TIM-4 SNPs) with systemic lupus erythematosus (SLE)susceptibility in a Chinese Han population.The results imply that GG genotype of the TIM-4 gene at -1419 site might be associated with the disease activity of SLE. (PMID:28371471)
• High expression of TIMD4 in clear cell renal cancer cells was closely related to short progression free survival time, and was associated with resistance to sorafenib. (PMID:28631038)
• Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells (PMID:28740388)
• These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for coronary heart disease and ischemic stroke (PMID:29208769)
• Up-regulated Tim-4 expression on monocytes or in plasma on day 2 was a risk predictor of outcome (PMID:29233585)
• Study results suggest that the TIMD4 rs6882076 single nucleotide polymorphism is associated with decreased risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Southern Chinese Han population. It is likely to decrease the CHD and IS risk by reducing serum triglycerides levels. (PMID:31337960)
• Tim4 regulates NALP3 inflammasome expression and activity during monocyte/macrophage dysfunction in septic shock patients. (PMID:31676250)
• The expression of Tim-1 and Tim-4 molecules in regulatory T cells in type 1 diabetes. (PMID:31916216)
• IL-6 in tumour microenvironment enhances TIM-4 expression in lung cancer cells via NF-kappaB, which in turn promotes metastasis and IL-6 production of lung cancer cells. (PMID:32020709)
• TIMD4 exhibits regulatory capability on the proliferation and apoptosis of diffuse large B-cell lymphoma cells via the Wnt/beta-catenin pathway. (PMID:32187802)
• Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis. (PMID:32640697)
• Autophagic adaptation to oxidative stress alters peritoneal residential macrophage survival and ovarian cancer metastasis. (PMID:32780724)
• Overexpression of Nuclear Enriched Autosomal Transcript 1 Facilitates Cell Proliferation, Migration Invasion, and Suppresses Apoptosis in Endometrial Cancer by Targeting MicroRNA-202-3p/T Cell Immunoglobulin and Mucin Domain 4 Axis. (PMID:32882142)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Timd4	ENSMUSG00000055546
rattus_norvegicus	Timd4	ENSRNOG00000038894
caenorhabditis_elegans		WBGENE00018289
caenorhabditis_elegans		WBGENE00020483
caenorhabditis_elegans		WBGENE00020484
caenorhabditis_elegans		WBGENE00020487
caenorhabditis_elegans		WBGENE00020785
caenorhabditis_elegans		WBGENE00021162
caenorhabditis_elegans		WBGENE00077592
caenorhabditis_elegans		WBGENE00195168
caenorhabditis_elegans		WBGENE00206360

Paralogs (3): HAVCR1 (ENSG00000113249), HAVCR2 (ENSG00000135077), MED7 (ENSG00000155868)

Protein

Protein identifiers

T-cell immunoglobulin and mucin domain-containing protein 4 — Q96H15 (reviewed: Q96H15)

Alternative names: T-cell immunoglobulin mucin receptor 4, T-cell membrane protein 4

All UniProt accessions (2): B5MCV9, Q96H15

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylserine receptor that plays different role in immune response including phagocytosis of apoptotic cells and T-cell regulation. Controls T-cell activation in a bimodal fashion, decreasing the activation of naive T-cells by inducing cell cycle arrest, while increasing proliferation of activated T-cells by activating AKT1 and ERK1/2 phosphorylations and subsequent signaling pathways. Also plays a role in efferocytosis which is the process by which apoptotic cells are removed by phagocytic cells. Mechanistically, promotes the engulfment of apoptotic cells or exogenous particles by securing them to phagocytes through direct binding to phosphatidylserine present on apoptotic cells, while other engulfment receptors such as MERTK efficiently recognize apoptotic cells and mediate their ingestion. Additionally, promotes autophagy process by suppressing NLRP3 inflammasome activity via activation of LKB1/PRKAA1 pathway in a phosphatidylserine-dependent mechanism. (Microbial infection) Plays a positive role in exosome-mediated trafficking of HIV-1 virus and its entry into immune cells.

Subunit / interactions. Interacts with MERTK; this interaction enhances TIMD4-mediated efferocytosis. Interacts with EPHA2.

Subcellular location. Cell membrane. Secreted. Extracellular exosome.

Domain organisation. Recognizes phosphatidyl serine via its immunoglobulin domain.

Similarity. Belongs to the immunoglobulin superfamily. TIM family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96H15-1	1	yes
Q96H15-2	2

RefSeq proteins (2): NP_001140198, NP_612388* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686

UniProt features (31 total): strand 10, disulfide bond 3, sequence variant 2, topological domain 2, helix 2, region of interest 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, sequence conflict 1, turn 1, transmembrane region 1, domain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5F7F	X-RAY DIFFRACTION	1.5
5DZN	X-RAY DIFFRACTION	2.3
5F7H	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96H15-F1	64.11	0.27

Functional residue map

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

Post-translational modifications (1): 358

Disulfide bonds (3): 40–112, 53–64, 59–111

Glycosylation sites (1): 291

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 78 (showing top): GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, TGCTGAY_UNKNOWN, IRF_Q6, GOBP_MEMBRANE_ORGANIZATION, GOBP_MEMBRANE_INVAGINATION, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, GOBP_PHAGOCYTOSIS, GOMF_PHOSPHATIDYLSERINE_BINDING, GOMF_MODIFIED_AMINO_ACID_BINDING, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING, PR_01, KYNG_NORMAL_AGING_DN

GO Biological Process (2): apoptotic cell clearance (GO:0043277), cytoskeletal rearrangement involved in phagocytosis, engulfment (GO:0060097)

GO Molecular Function (1): phosphatidylserine binding (GO:0001786)

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
phagocytosis	1
phagocytosis, engulfment	1
cytoskeleton organization	1
phospholipid binding	1
anion binding	1
modified amino acid binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIMD4	ADGRB1	O14514	852
TIMD4	HAVCR1	Q96D42	846
TIMD4	STAB2	Q8WWQ8	820
TIMD4	GAS6	Q14393	804
TIMD4	TYRO3	Q06418	721
TIMD4	JMJD6	Q6NYC1	708
TIMD4	MERTK	Q12866	694
TIMD4	SCARB2	Q14108	682
TIMD4	CD36	P16671	681
TIMD4	MFGE8	Q08431	661
TIMD4	SCARB1	Q8WTV0	660
TIMD4	CLEC4F	Q8N1N0	642
TIMD4	CD300LB	A8K4G0	622
TIMD4	AXL	P30530	614
TIMD4	STAB1	Q9NY15	608

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CD300LF	TIMD4	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	TIMD4	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	TIMD4	psi-mi:“MI:0915”(physical association)	0.400
CFTR	TIMD4	psi-mi:“MI:0915”(physical association)	0.370
TIMD4	SEMG1	psi-mi:“MI:0914”(association)	0.350
TIMD4	ST3GAL3	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): FN1 (Two-hybrid), TIMD4 (Reconstituted Complex), TIMD4 (Affinity Capture-Western), TIMD4 (Co-localization), TIMD4 (Affinity Capture-Western), TIMD4 (Proximity Label-MS), GALT (Affinity Capture-MS), SERPINB9 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), ST3GAL3 (Affinity Capture-MS), SPATA5 (Affinity Capture-MS), CINP (Affinity Capture-MS), SPRR3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y7Y5, A1KXC4, A6QLF8, J3KML8, O00592, O35188, O55145, O57604, P06484, P07141, P13838, P14220, P15702, P16150, P18827, P20934, P26260, P34740, P47951, P59647, P78423, P97808, Q08DZ5, Q1ECS6, Q28270, Q28645, Q29RT9, Q3MIW9, Q3TNW5, Q52S86, Q58Y74, Q5RAF8, Q62170, Q64314, Q6MG22, Q6P9X9, Q6UWI2, Q6UXF1, Q86YL7, Q8BHE4

Diamond homologs: O46598, O54947, P0C0K5, Q5FVR0, Q5QNS5, Q6U7R4, Q8R183, Q8TDQ0, Q8VIM0, Q96D42, Q96H15, Q3V3F6, Q6UWV2, A4QPC6, P78310, P97792, Q5R764, Q9R066, Q6ZMC9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	39
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2425364	NC_000005.9:g.(?155338082)(156899968_?)del	Pathogenic

SpliceAI

1127 predictions. Top by Δscore:

Variant	Effect	Δscore
5:156922212:TCCAT:T	acceptor_gain	1.0000
5:156922213:CCAT:C	acceptor_gain	1.0000
5:156922213:CCATC:C	acceptor_gain	1.0000
5:156922214:CAT:C	acceptor_gain	1.0000
5:156922214:CATC:C	acceptor_gain	1.0000
5:156922216:TC:T	acceptor_loss	1.0000
5:156922217:C:CC	acceptor_gain	1.0000
5:156922226:C:CT	acceptor_gain	1.0000
5:156922228:C:CT	acceptor_gain	1.0000
5:156922229:A:T	acceptor_gain	1.0000
5:156950810:AACC:A	donor_gain	1.0000
5:156951507:CGTA:C	donor_loss	1.0000
5:156951508:GTAC:G	donor_loss	1.0000
5:156951511:C:CT	donor_loss	1.0000
5:156951532:T:TA	donor_gain	1.0000
5:156951568:T:TA	donor_gain	1.0000
5:156951789:GG:G	acceptor_gain	1.0000
5:156951789:GGCTG:G	acceptor_loss	1.0000
5:156951790:GCTG:G	acceptor_loss	1.0000
5:156951791:C:A	acceptor_loss	1.0000
5:156951791:C:CC	acceptor_gain	1.0000
5:156954409:GCTTA:G	donor_loss	1.0000
5:156954410:CTTAC:C	donor_loss	1.0000
5:156954411:TTAC:T	donor_loss	1.0000
5:156954412:TA:T	donor_loss	1.0000
5:156954414:CCT:C	donor_gain	1.0000
5:156954414:CCTCT:C	donor_gain	1.0000
5:156919537:CTAGC:C	acceptor_gain	0.9900
5:156919538:TAGC:T	acceptor_gain	0.9900
5:156919540:GCC:G	acceptor_loss	0.9900

AlphaMissense

2441 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:156954653:C:A	W54C	0.999
5:156954653:C:G	W54C	0.999
5:156954525:A:G	L97S	0.994
5:156954477:C:G	R113P	0.991
5:156954480:C:G	C112S	0.990
5:156954481:A:T	C112S	0.990
5:156954655:A:G	W54R	0.989
5:156954655:A:T	W54R	0.989
5:156954519:A:G	I99T	0.985
5:156954564:T:C	Y84C	0.984
5:156954480:C:T	C112Y	0.983
5:156954680:C:A	W45C	0.983
5:156954680:C:G	W45C	0.983
5:156954696:C:G	C40S	0.983
5:156954697:A:T	C40S	0.983
5:156954455:G:C	F120L	0.982
5:156954455:G:T	F120L	0.982
5:156954457:A:G	F120L	0.982
5:156954486:T:C	Y110C	0.982
5:156954702:A:G	L38S	0.982
5:156954479:G:C	C112W	0.981
5:156954624:C:G	C64S	0.981
5:156954625:A:T	C64S	0.981
5:156954639:C:G	C59S	0.981
5:156954640:A:T	C59S	0.981
5:156954695:A:C	C40W	0.981
5:156954657:C:G	C53S	0.978
5:156954658:A:T	C53S	0.978
5:156954525:A:C	L97W	0.977
5:156954487:A:C	Y110D	0.976

dbSNP variants (sampled 300 via entrez): RS1000049921 (5:156931639 A>G), RS1000092440 (5:156950438 G>A,T), RS1000126875 (5:156944104 C>T), RS1000143931 (5:156943367 T>A), RS1000148924 (5:156944321 G>C), RS1000177723 (5:156937273 T>C), RS1000186227 (5:156921688 C>A,T), RS1000196971 (5:156943025 G>C), RS1000305931 (5:156938181 C>T), RS1000362479 (5:156938471 T>A,C), RS1000559374 (5:156925427 C>G), RS1000580815 (5:156926596 T>G), RS1000634322 (5:156937624 C>T), RS1000728481 (5:156920205 A>G), RS1000744872 (5:156941594 G>T)

Disease associations

OMIM: gene MIM:610096 | disease phenotypes: MIM:613011

GenCC curated gene-disease

Mondo (1): lymphoproliferative syndrome 1 (MONDO:0013081)

Orphanet (2): Combined immunodeficiency due to CD27 deficiency (Orphanet:238505), Combined immunodeficiency due to ITK deficiency (Orphanet:538963)

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000287_11	LDL cholesterol	1.000000e-11
GCST000758_18	Triglycerides	4.000000e-12
GCST000759_14	LDL cholesterol	2.000000e-22
GCST000760_10	Cholesterol, total	7.000000e-28
GCST001905_8	Hypertriglyceridemia	3.000000e-06
GCST002216_6	Triglycerides	2.000000e-15
GCST002221_40	Cholesterol, total	5.000000e-41
GCST002222_1	LDL cholesterol	3.000000e-31
GCST002896_15	Cholesterol, total	2.000000e-21
GCST002897_25	Triglycerides	2.000000e-11
GCST002898_14	LDL cholesterol	2.000000e-15
GCST004233_40	LDL cholesterol levels	1.000000e-33
GCST004235_22	Total cholesterol levels	2.000000e-43
GCST004237_39	Triglyceride levels	3.000000e-16
GCST004607_240	Plateletcrit	4.000000e-09
GCST006004_12	Low density lipoprotein cholesterol levels	1.000000e-08
GCST006034_34	Total cholesterol levels	3.000000e-16
GCST007931_17	Medication use (HMG CoA reductase inhibitors)	2.000000e-12
GCST009365_55	LDL cholesterol levels x short total sleep time interaction (2df test)	8.000000e-10
GCST009366_55	LDL cholesterol levels x long total sleep time interaction (2df test)	1.000000e-16
GCST010173_45	Triglyceride levels	1.000000e-38
GCST010243_177	Apolipoprotein B levels	1.000000e-47
GCST010244_31	Triglyceride levels	2.000000e-57
GCST010245_228	LDL cholesterol levels	1.000000e-50
GCST011345_4	Triglyceride levels	6.000000e-14
GCST011346_20	Total cholesterol levels	3.000000e-23
GCST011347_22	Low density lipoprotein cholesterol levels	1.000000e-13
GCST90002400_653	Plateletcrit	2.000000e-16
GCST90002402_711	Platelet count	5.000000e-19

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0007985	platelet crit
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567815	Lymphoproliferative Syndrome, Ebv-Associated, Autosomal, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	affects methylation	1
Copper Sulfate	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1KJ	HyCyte HEK293T KO-hTIMD4	Transformed cell line	Female

Clinical trials (associated diseases)

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