CD96

Summary

CD96 (CD96 molecule, HGNC:16892) is a protein-coding gene on chromosome 3q13.13-q13.2, encoding T-cell surface protein tactile (P40200). May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response.

The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein. The protein may play a role in the adhesive interactions of activated T and NK cells during the late phase of the immune response. It may also function in antigen presentation. Alternative splicing generates multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 10225 — RefSeq curated summary.

At a glance

• Gene–disease (curated): C syndrome (Limited, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 245 total — 2 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 79
• MANE Select transcript: NM_005816

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16892
Approved symbol	CD96
Name	CD96 molecule
Location	3q13.13-q13.2
Locus type	gene with protein product
Status	Approved
Aliases	TACTILE
Ensembl gene	ENSG00000153283
Ensembl biotype	protein_coding
OMIM	606037
Entrez	10225

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 nonsense_mediated_decay

ENST00000283285, ENST00000352690, ENST00000438817, ENST00000460744, ENST00000465428, ENST00000488054, ENST00000494798, ENST00000862454, ENST00000862455, ENST00000862456, ENST00000862457, ENST00000862458, ENST00000862459, ENST00000862460

RefSeq mRNA: 4 — MANE Select: NM_005816 NM_001318889, NM_001410800, NM_005816, NM_198196

CCDS: CCDS2958, CCDS2959, CCDS82817, CCDS93339

Canonical transcript exons

ENST00000352690 — 14 exons

Exon	Start	End
ENSE00001009963	111585323	111585378
ENSE00001009964	111579027	111579234
ENSE00001075762	111545046	111545402
ENSE00001236596	111647543	111647666
ENSE00001236600	111638079	111638168
ENSE00001236610	111637196	111637261
ENSE00001236616	111624333	111624404
ENSE00001236622	111623754	111623822
ENSE00001236631	111606700	111606792
ENSE00001236639	111600726	111600914
ENSE00001236651	111598120	111598210
ENSE00001838677	111542197	111542309
ENSE00003536914	111567523	111567647
ENSE00003694913	111649698	111652372

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 93.05.

FANTOM5 (CAGE): breadth broad, TPM avg 8.5194 / max 509.7640, expressed in 306 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37870	4.4779	228
37869	3.1963	203
37868	0.6826	121
37867	0.1345	64
37865	0.0281	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.05	gold quality
lymph node	UBERON:0000029	87.59	gold quality
blood	UBERON:0000178	86.38	gold quality
spleen	UBERON:0002106	82.23	gold quality
vermiform appendix	UBERON:0001154	81.74	gold quality
colonic epithelium	UBERON:0000397	81.40	gold quality
gall bladder	UBERON:0002110	79.61	gold quality
rectum	UBERON:0001052	79.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.75	gold quality
mucosa of transverse colon	UBERON:0004991	78.02	gold quality
bone marrow cell	CL:0002092	76.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.49	silver quality
small intestine	UBERON:0002108	76.30	gold quality
thymus	UBERON:0002370	75.72	silver quality
upper lobe of left lung	UBERON:0008952	74.87	gold quality
tonsil	UBERON:0002372	74.69	gold quality
caecum	UBERON:0001153	74.67	gold quality
omental fat pad	UBERON:0010414	74.44	gold quality
peritoneum	UBERON:0002358	74.35	gold quality
upper lobe of lung	UBERON:0008948	73.92	gold quality
adipose tissue of abdominal region	UBERON:0007808	73.15	gold quality
right lung	UBERON:0002167	72.41	gold quality
amniotic fluid	UBERON:0000173	72.33	gold quality
leukocyte	CL:0000738	72.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.24	gold quality
bone marrow	UBERON:0002371	72.00	gold quality
left lobe of thyroid gland	UBERON:0001120	70.83	gold quality
thyroid gland	UBERON:0002046	70.14	gold quality
mononuclear cell	CL:0000842	70.10	gold quality
duodenum	UBERON:0002114	69.84	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	105.54
E-MTAB-6701	yes	88.96
E-CURD-88	yes	51.75
E-CURD-122	yes	42.22
E-CURD-46	yes	35.70
E-MTAB-10287	yes	32.15
E-MTAB-6678	yes	26.71
E-MTAB-8410	yes	12.65
E-HCAD-10	yes	9.52
E-HCAD-1	yes	5.85
E-MTAB-9067	yes	5.52
E-CURD-112	yes	5.02
E-CURD-135	no	901.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting CD96, 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-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-1322	97.98	68.96	625
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-5694	97.06	67.70	682

Literature-anchored findings (GeneRIF, showing 25)

• CD96 promotes natural killer (NK) cell adhesion to target cells expressing the poliovirus receptor (PVR), stimulates cytotoxicity of activated NK cells, and mediates acquisition of PVR from target cells. (PMID:15034010)
• CD96 is a cell surface marker present on many acute myeloid leukemia leukemic stem cells (PMID:17576927)
• CD96-driven adhesion to CD155 may be crucial in developmental processes (PMID:19056733)
• The positive expression of CD96 on bone marrow hematopoietic stem cells in patients with acute leukemia may be associated with primary drug resistance, relapse and progression. (PMID:21729528)
• CD96 could serve as a target structure for effector cell-mediated lysis. (PMID:22879978)
• down-regulation of CD96 is an important aspect of HIV-1 pathogenesis and differential expression is related to cell effector functions and HIV-1 disease course. (PMID:23272144)
• In the present study we analyzed the expression of four cell surface antigens relevant to human hematopoiesis-CD90, CD96, CD117, and CD123-in bone marrow from pediatric acute myeloid leukemia patients and normal control subjects. (PMID:24751333)
• CD96 and CD123 are expressed in bone marrow cells of patients with myelodysplastic syndromes (PMID:26642704)
• Blocking CD96 or TIGIT with mAbs has been shown to improve tumor control in mice. (PMID:27620276)
• Lower CD96 expression was also observed in human IL-9(+) compared with IFN-gamma(+) T cells (PMID:29531070)
• CD96 expression was highly correlated with T-cell markers in primary and metastatic human tumors and was elevated on antigen-experienced T cells and tumor-infiltrating lymphocytes. Collectively, these data demonstrate that CD96 may be a promising immune checkpoint to enhance T-cell function against human cancer and infectious disease (PMID:30222899)
• increased expression on intratumoral natural killer cells of hepatocellular carcinoma patients (PMID:30411378)
• Results show that the first immunoglobulin domain (D1) of CD96 is sufficient to mediate a robust interaction with necl-5, but not the DNAM-1 and TIGIT ligand, nectin-2. The crystal structure of CD96-D1 bound to the necl-5 ectodomain revealed that CD96 recognized necl-5 D1 via a conserved “lock-and-key” interaction observed across TIGIT:necl complexes. (PMID:30528596)
• Nectin-1 directly interacts with CD96 in vitro. The binding site for CD96 is located on the nectin-1 V-domain, which comprises a canonical interface that is shared by nectins to promote cell adhesion. The affinity of nectin-1 for CD96 is lower than for other nectins such as nectin-3 and nectin-1 itself. (PMID:30759143)
• CD96 functions as a co-stimulatory receptor to enhance CD8(+) T cell activation and effector responses. (PMID:32043568)
• CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma. (PMID:32612110)
• Direct interaction between CD155 and CD96 promotes immunosuppression in lung adenocarcinoma. (PMID:32917981)
• Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy. (PMID:33298247)
• Early expression of CD94 and loss of CD96 on CD8+ T cells after allogeneic stem cell tranplantation is predictive of subsequent relapse and survival. (PMID:35924575)
• Natural killer cell profiles in recurrent pregnancy loss: Increased expression and positive associations with TACTILE and LILRB1. (PMID:36004818)
• Tumor Cell-Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid beta-Oxidation. (PMID:36581470)
• CD96 as a Potential Immune Regulator in Cancers. (PMID:36674817)
• CD44, CD90 and CD96 expression in immune thrombocytopenia purpura (ITP) patients. (PMID:36949573)
• Deficiency of the CD155-CD96 immune checkpoint controls IL-9 production in giant cell arteritis. (PMID:37075705)
• Prognostic impact of enhanced CD96 expression on NK cells by TGF-beta1 in AML. (PMID:39159564)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch1073-15f19.2	ENSDARG00000095640
mus_musculus	Cd96	ENSMUSG00000022657
rattus_norvegicus	Cd96	ENSRNOG00000023030

Protein

Protein identifiers

T-cell surface protein tactile — P40200 (reviewed: P40200)

Alternative names: Cell surface antigen CD96, T cell-activated increased late expression protein

All UniProt accessions (6): P40200, E9PEJ1, F8WDV3, H7C4F0, Q8WUE2, U3KPT0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response. Promotes NK cell-target adhesion by interacting with PVR present on target cells. May function at a time after T and NK cells have penetrated the endothelium using integrins and selectins, when they are actively engaging diseased cells and moving within areas of inflammation.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with PVR.

Subcellular location. Membrane.

Tissue specificity. Expressed on normal T-cell lines and clones, and some transformed T-cells, but no other cultured cell lines tested. It is expressed at very low levels on activated B-cells.

Disease relevance. C syndrome (CSYN) [MIM:211750] A syndrome characterized by trigonocephaly, severe intellectual disability, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving CD96 has been found in a patient with C syndrome. Translocation t(3;18)(q13.13;q12.1). CD96 gene was located at the 3q13.13 breakpoint. Precise structural analysis around the breakpoint showed that the gene was disrupted by the translocation in exon 5, probably leading to premature termination or loss of expression of CD96 protein. No gene was detected at the chromosome 18 breakpoint.

Isoforms (2)

UniProt ID	Names	Canonical?
P40200-1	1	yes
P40200-2	2

RefSeq proteins (4): NP_001305818, NP_001397729, NP_005807, NP_937839 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR042381	CD96	Family

UniProt features (44 total): glycosylation site 15, strand 8, compositionally biased region 3, disulfide bond 3, turn 3, domain 3, topological domain 2, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ARQ	X-RAY DIFFRACTION	2.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40200-F1	65.81	0.19

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 (3): 45–118, 163–247, 290–355

Glycosylation sites (15): 42, 97, 107, 148, 156, 166, 200, 215, 277, 278, 300, 350, 368, 435, 497

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 463 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, MODULE_64, GOBP_NEGATIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GNF2_ZAP70, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_TYPE_II_INTERFERON_PRODUCTION

GO Biological Process (7): negative regulation of natural killer cell cytokine production (GO:0002728), inflammatory response (GO:0006954), immune response (GO:0006955), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), response to lipopolysaccharide (GO:0032496), negative regulation of type II interferon production (GO:0032689)

GO Molecular Function (0):

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
natural killer cell cytokine production	1
negative regulation of natural killer cell mediated immunity	1
negative regulation of cytokine production involved in immune response	1
regulation of natural killer cell cytokine production	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
cell-substrate adhesion	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
negative regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD96	NECTIN2	Q92692	999
CD96	PVR	P15151	999
CD96	NECTIN1	Q15223	992
CD96	TIGIT	Q495A1	967
CD96	NCR3	O14931	776
CD96	KLRC1	P26715	759
CD96	NCR1	O76036	747
CD96	LAG3	P18627	725
CD96	CTLA4	P16410	713
CD96	CD226	Q15762	673
CD96	PVRIG	Q6DKI7	667
CD96	HAVCR2	Q8TDQ0	663
CD96	NECTIN3	Q9NQS3	614
CD96	IL15	P40933	603
CD96	LILRB1	Q8NHL6	600

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CD96	PVR	psi-mi:“MI:0914”(association)	0.700
PVR	CD96	psi-mi:“MI:0915”(physical association)	0.700
CD96	PVR	psi-mi:“MI:0407”(direct interaction)	0.700
CD96	SQSTM1	psi-mi:“MI:0914”(association)	0.350
TMEM260	MYH3	psi-mi:“MI:0914”(association)	0.350
cpfC1	CD96	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): UBR4 (Affinity Capture-MS), LAMB1 (Affinity Capture-MS), FAT1 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), TMEM160 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), CLSTN1 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), PXDN (Affinity Capture-MS), GBAS (Affinity Capture-MS), PVR (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y4Y8, A0A2R8YFL7, A0A2R8YFM6, A0A8J1K1A4, A5D791, E7FKV8, O77726, O88393, P20239, P20783, P26342, P35054, P40200, P47984, Q03167, Q05996, Q08DT3, Q17R60, Q2Q0J1, Q3MHP9, Q3U0X8, Q3V1M1, Q4FZG8, Q4V7E2, Q5BK49, Q5SY80, Q5XI99, Q6DFV8, Q6WRH9, Q6WRI0, Q6X784, Q7TST5, Q80VH0, Q86WS3, Q8JIR8, Q8R1W8, Q925U0, Q95KG7, Q9D9J7, Q9ET62

Diamond homologs: P40200, Q3MHP9, Q3U0X8, Q5BK49, O46634, O46651, Q9EPF2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	165
Likely benign	46
Benign	9

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
4639	46,XY t(3;18)(q13.13;q12.1)	Pathogenic
4640	NM_005816.5(CD96):c.791C>T (p.Thr264Met)	Pathogenic
3899989	NM_005816.5(CD96):c.537del (p.Trp179fs)	Likely pathogenic
3899990	NM_005816.5(CD96):c.1199C>G (p.Ser400Ter)	Likely pathogenic
4277501	NM_005816.5(CD96):c.807+2T>A	Likely pathogenic
4277502	NM_005816.5(CD96):c.1321+1G>A	Likely pathogenic

SpliceAI

2662 predictions. Top by Δscore:

Variant	Effect	Δscore
3:111542306:AAGGG:A	donor_loss	1.0000
3:111542307:AGGG:A	donor_loss	1.0000
3:111542308:GG:G	donor_gain	1.0000
3:111542308:GGGTA:G	donor_loss	1.0000
3:111542309:GG:G	donor_gain	1.0000
3:111545040:TTTCA:T	acceptor_loss	1.0000
3:111545041:TTCA:T	acceptor_loss	1.0000
3:111545044:A:AG	acceptor_gain	1.0000
3:111545044:AG:A	acceptor_gain	1.0000
3:111545045:G:GA	acceptor_gain	1.0000
3:111545045:GG:G	acceptor_gain	1.0000
3:111545045:GGA:G	acceptor_gain	1.0000
3:111545045:GGAGT:G	acceptor_gain	1.0000
3:111585321:A:G	acceptor_gain	1.0000
3:111595298:A:AC	donor_gain	1.0000
3:111595299:C:CC	donor_gain	1.0000
3:111595299:CAA:C	donor_gain	1.0000
3:111595299:CAAG:C	donor_gain	1.0000
3:111624406:T:G	donor_gain	1.0000
3:111636299:G:GT	donor_gain	1.0000
3:111636300:A:T	donor_gain	1.0000
3:111637195:GCA:G	acceptor_gain	1.0000
3:111647537:TTTCA:T	acceptor_loss	1.0000
3:111647538:TTCA:T	acceptor_loss	1.0000
3:111647539:TCAGG:T	acceptor_loss	1.0000
3:111647540:CA:C	acceptor_loss	1.0000
3:111647541:A:T	acceptor_loss	1.0000
3:111647542:G:T	acceptor_loss	1.0000
3:111647648:GTC:G	donor_gain	1.0000
3:111647662:GAAAT:G	donor_gain	1.0000

AlphaMissense

3739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:111545156:T:A	W58R	0.989
3:111545156:T:C	W58R	0.989
3:111598171:T:A	W303R	0.988
3:111598171:T:C	W303R	0.988
3:111545158:G:C	W58C	0.987
3:111545158:G:T	W58C	0.987
3:111545159:T:C	S59P	0.983
3:111598132:T:C	C290R	0.983
3:111649717:T:C	F557L	0.982
3:111649719:C:A	F557L	0.982
3:111649719:C:G	F557L	0.982
3:111545112:T:C	L43P	0.978
3:111598134:C:G	C290W	0.977
3:111600842:T:A	C355S	0.977
3:111600843:G:C	C355S	0.977
3:111545154:A:C	Q57P	0.976
3:111600842:T:C	C355R	0.975
3:111598132:T:A	C290S	0.974
3:111598133:G:C	C290S	0.974
3:111545292:T:C	L103P	0.972
3:111649722:G:C	K558N	0.971
3:111649722:G:T	K558N	0.971
3:111598173:G:C	W303C	0.970
3:111598173:G:T	W303C	0.970
3:111545336:T:A	C118S	0.969
3:111545337:G:C	C118S	0.969
3:111545330:T:G	Y116D	0.968
3:111545336:T:C	C118R	0.968
3:111600782:T:C	S335P	0.966
3:111600844:T:G	C355W	0.966

dbSNP variants (sampled 300 via entrez): RS1000020456 (3:111625791 C>T), RS1000021044 (3:111549194 C>A), RS1000033962 (3:111651924 T>C), RS1000042829 (3:111662473 G>T), RS1000072551 (3:111589096 G>A,T), RS1000086790 (3:111541884 A>G), RS1000136899 (3:111631703 C>A), RS1000151160 (3:111571401 T>A), RS1000153077 (3:111615258 A>G), RS1000186412 (3:111590492 A>T), RS1000198044 (3:111608665 T>C), RS1000202084 (3:111627018 T>C), RS1000211329 (3:111650351 C>A,G), RS1000218965 (3:111616582 C>T), RS1000241984 (3:111588740 T>G)

Disease associations

OMIM: gene MIM:606037 | disease phenotypes: MIM:211750

GenCC curated gene-disease

Disease	Classification	Inheritance
C syndrome	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
C syndrome	Limited	AD

Mondo (1): C syndrome (MONDO:0008893)

Orphanet (1): C syndrome (Orphanet:1308)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000085	Horseshoe kidney
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000191	Accessory oral frenulum
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000582	Upslanted palpebral fissure
HP:0000767	Pectus excavatum
HP:0000776	Congenital diaphragmatic hernia
HP:0000803	Renal cortical cysts
HP:0000960	Sacral dimple
HP:0000973	Cutis laxa
HP:0001161	Hand polydactyly
HP:0001162	Postaxial hand polydactyly

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001111_1	Current cigarettes per day in chronic obstructive pulmonary disease	1.000000e-07
GCST008271_1	Anti-adalimumab antibody production in response to treatment in Crohn’s disease	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537418	Opitz trigonocephaly syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, decreases expression, affects cotreatment	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Asian ginseng	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression, affects cotreatment	1
Troglitazone	increases expression	1
Homoharringtonine	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Allergens	affects cotreatment, increases expression	1
Vehicle Emissions	increases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Cyclosporine	increases methylation	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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