CNTNAP4

Summary

CNTNAP4 (contactin associated protein family member 4, HGNC:18747) is a protein-coding gene on chromosome 16q23.1, encoding Contactin-associated protein-like 4 (Q9C0A0). Presynaptic protein involved in both dopaminergic synaptic transmission and GABAergic system, thereby participating in the structural maturation of inhibitory interneuron synapses.

This gene encodes a member of the neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity.

Source: NCBI Gene 85445 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 124 total
• Druggable target: yes
• MANE Select transcript: NM_033401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18747
Approved symbol	CNTNAP4
Name	contactin associated protein family member 4
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Aliases	CASPR4, KIAA1763
Ensembl gene	ENSG00000152910
Ensembl biotype	protein_coding
OMIM	610518
Entrez	85445

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000307431, ENST00000377504, ENST00000463177, ENST00000471618, ENST00000476707, ENST00000478060, ENST00000611870, ENST00000619533, ENST00000622250, ENST00000867848, ENST00000867849, ENST00000867850, ENST00000867851, ENST00000958512

RefSeq mRNA: 11 — MANE Select: NM_033401 NM_001322178, NM_001322179, NM_001322180, NM_001322181, NM_001322187, NM_001322188, NM_001322189, NM_001322190, NM_001322191, NM_033401, NM_138994

CCDS: CCDS10924, CCDS73915, CCDS82015

Canonical transcript exons

ENST00000611870 — 24 exons

Exon	Start	End
ENSE00003459878	76489686	76489883
ENSE00003463987	76316413	76316523
ENSE00003499104	76449715	76449858
ENSE00003500338	76461956	76462105
ENSE00003521161	76475939	76476045
ENSE00003526224	76355318	76355511
ENSE00003536369	76427452	76427599
ENSE00003547195	76452508	76452769
ENSE00003575351	76539719	76539852
ENSE00003581565	76498567	76498694
ENSE00003586657	76467352	76467523
ENSE00003593268	76521140	76521310
ENSE00003606156	76479419	76479538
ENSE00003618991	76553283	76553501
ENSE00003630128	76535545	76535784
ENSE00003632308	76448012	76448215
ENSE00003650642	76540703	76540790
ENSE00003651196	76522039	76522257
ENSE00003661360	76553836	76553907
ENSE00003680735	76448767	76448951
ENSE00003681828	76538116	76538340
ENSE00003683344	76494910	76495066
ENSE00003845174	76277401	76277747
ENSE00003845595	76558490	76560757

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 98.32.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7376 / max 2333.7886, expressed in 198 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155052	3.1859	140
155050	1.3015	101
155054	0.6677	146
155051	0.3270	74
155047	0.1789	70
155053	0.0426	22
155055	0.0340	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.32	gold quality
spinal cord	UBERON:0002240	98.00	gold quality
corpus callosum	UBERON:0002336	97.82	gold quality
endothelial cell	CL:0000115	97.06	gold quality
inferior vagus X ganglion	UBERON:0005363	95.49	gold quality
pons	UBERON:0000988	94.85	gold quality
substantia nigra	UBERON:0002038	94.42	gold quality
midbrain	UBERON:0001891	94.22	gold quality
subthalamic nucleus	UBERON:0001906	92.84	gold quality
medulla oblongata	UBERON:0001896	92.69	gold quality
hypothalamus	UBERON:0001898	92.14	gold quality
cerebellar hemisphere	UBERON:0002245	92.03	gold quality
cerebellar cortex	UBERON:0002129	92.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.74	gold quality
cerebellum	UBERON:0002037	91.66	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.55	gold quality
Ammon’s horn	UBERON:0001954	91.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.43	gold quality
superior vestibular nucleus	UBERON:0007227	90.28	gold quality
ventral tegmental area	UBERON:0002691	90.01	gold quality
prefrontal cortex	UBERON:0000451	89.87	gold quality
amygdala	UBERON:0001876	89.17	gold quality
medial globus pallidus	UBERON:0002477	89.16	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.09	gold quality
frontal cortex	UBERON:0001870	88.06	gold quality
frontal lobe	UBERON:0016525	88.06	gold quality
globus pallidus	UBERON:0001875	87.74	gold quality
right frontal lobe	UBERON:0002810	87.63	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.52	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	72.40
E-HCAD-25	yes	54.44
E-ANND-3	yes	6.36
E-CURD-11	no	75.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting CNTNAP4, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
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-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
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-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3919	99.87	69.45	2489

Literature-anchored findings (GeneRIF, showing 5)

• A quantitative analysis of central corneal thickness and a subsequent analysis of primary open-angle glaucoma (POAG), SNPs in two cell adhesion molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility in a subset of cases. (PMID:22661486)
• This study is the first demonstration for association of the CNTNAP4 gene and one of its intronic CNV polymorphisms with aging. (PMID:24223195)
• we demonstrated that the expression of contactin-associated protein-like 4 (CNTNAP4) was decreased in the temporal neocortex of epileptic patients (PMID:28968899)
• CNTNAP4 deficiency in dopaminergic neurons initiates parkinsonian phenotypes. (PMID:32194851)
• Early B Cell Factor 3 (EBF3) attenuates Parkinson’s disease through directly regulating contactin-associated protein-like 4 (CNTNAP4) transcription: An experimental study. (PMID:38479556)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cntnap4	ENSMUSG00000031772
rattus_norvegicus	Cntnap4	ENSRNOG00000011231

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Contactin-associated protein-like 4 — Q9C0A0 (reviewed: Q9C0A0)

Alternative names: Cell recognition molecule Caspr4

All UniProt accessions (5): Q9C0A0, A0A087WTA1, A0A0A0MR20, E9PDN6, F5H107

UniProt curated annotations — full annotation on UniProt →

Function. Presynaptic protein involved in both dopaminergic synaptic transmission and GABAergic system, thereby participating in the structural maturation of inhibitory interneuron synapses. Involved in the dopaminergic synaptic transmission by attenuating dopamine release through a presynaptic mechanism. Also participates in the GABAergic system.

Subunit / interactions. Interacts with TIAM1.

Subcellular location. Presynaptic cell membrane.

Similarity. Belongs to the neurexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0A0-1	1	yes
Q9C0A0-2	2

RefSeq proteins (11): NP_001309107, NP_001309108, NP_001309109, NP_001309110, NP_001309116, NP_001309117, NP_001309118, NP_001309119, NP_001309120, NP_207837, NP_620481 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR000742	EGF	Domain
IPR001791	Laminin_G	Domain
IPR002181	Fibrinogen_a/b/g_C_dom	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR036056	Fibrinogen-like_C	Homologous_superfamily
IPR050372	Neurexin-related_CASP	Family

Pfam: PF00754, PF02210

UniProt features (45 total): glycosylation site 12, disulfide bond 11, domain 8, sequence variant 5, topological domain 2, splice variant 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4NXQ	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0A0-F1	83.67	0.58

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 (11): 31–177, 332–364, 515–547, 553–564, 558–573, 575–585, 931–958, 962–975, 969–984, 986–996, 1167–1202

Glycosylation sites (12): 260, 285, 359, 538, 574, 602, 625, 637, 706, 748, 1023, 1073

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): YAATNRNNNYNATT_UNKNOWN, GOBP_BEHAVIOR, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GTACAGG_MIR486, FOXD3_01, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_BEHAVIOR, NF1_Q6_01, GOBP_SYNAPTIC_TRANSMISSION_DOPAMINERGIC, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, OCT1_07, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_SYNAPTIC_SIGNALING, GOBP_GROOMING_BEHAVIOR

GO Biological Process (5): cell adhesion (GO:0007155), nervous system development (GO:0007399), regulation of synaptic transmission, dopaminergic (GO:0032225), regulation of synaptic transmission, GABAergic (GO:0032228), regulation of grooming behavior (GO:2000821)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): presynaptic membrane (GO:0042734), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
modulation of chemical synaptic transmission	2
cellular anatomical structure	2
cellular process	1
system development	1
synaptic transmission, dopaminergic	1
synaptic transmission, GABAergic	1
grooming behavior	1
regulation of behavior	1
binding	1
synaptic membrane	1
presynapse	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

1508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNTNAP4	CNTN5	O94779	955
CNTNAP4	NRCAM	Q92823	862
CNTNAP4	APBA1	Q02410	678
CNTNAP4	EPB41	P11171	667
CNTNAP4	CHL1	O00533	665
CNTNAP4	TIAM1	Q13009	513
CNTNAP4	NFASC	O94856	504
CNTNAP4	CDH9	Q9ULB4	503
CNTNAP4	MEGF10	Q96KG7	463
CNTNAP4	ATP2C2	O75185	455
CNTNAP4	CDH8	P55286	448
CNTNAP4	CNTN4	Q8IWV2	434
CNTNAP4	SLC17A8	Q8NDX2	432
CNTNAP4	CNTN6	Q9UQ52	430
CNTNAP4	DYNLRB2	Q8TF09	430

IntAct

131 interactions, top by confidence:

A	B	Type	Score
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
CNTNAP4	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	PARD3	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	MPP7	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	DVL3	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	CNTNAP4	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
APBA1	CNTNAP4	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
APBA2	CNTNAP4	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (24): CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CASK (Reconstituted Complex), APBA1 (Reconstituted Complex), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS), CNTNAP4 (Affinity Capture-MS)

ESM2 similar proteins: A1XQX0, A1XQX2, A1XQX8, A1XQY1, A3KN33, B4F785, B8UU78, D0PRN3, E9Q7X7, P12080, P29319, P29320, P54764, Q02763, Q02858, Q03137, Q06807, Q07310, Q07496, Q0V8S9, Q0V8T0, Q0V8T3, Q0V8T4, Q0V8T5, Q0V8T6, Q0V8T7, Q0V8T8, Q0V8T9, Q19617, Q28146, Q3KN41, Q4VBE4, Q5RD64, Q63372, Q63374, Q63HQ2, Q6P9K9, Q8QFX6, Q8WYK1, Q91694

Diamond homologs: A2VEC9, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, G5ECS8, O08721, O08722, O08747, O14514, O15072, O60241, O60242, O75173, O95185, O95450, P07358, P07996, P10643, P11680, P27918, P35440, P35441, P35442, P35446, P35447, P35448, P55314, P57110, P58397, P59384, P79331, P82987, P98137, P98167, Q03350

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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	47.6×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	45.3×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	45.3×	3e-06
Assembly and cell surface presentation of NMDA receptors	10	42.3×	2e-12
Dopamine Neurotransmitter Release Cycle	5	41.4×	4e-06
Long-term potentiation	5	39.6×	4e-06
Neurexins and neuroligins	11	36.1×	1e-12
Protein-protein interactions at synapses	7	31.0×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	72.6×	7e-16
protein localization to synapse	6	52.2×	2e-07
receptor clustering	7	49.6×	2e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	33.8×	2e-06
protein-containing complex assembly	9	11.7×	5e-06
cell-cell adhesion	10	11.5×	2e-06
regulation of small GTPase mediated signal transduction	5	8.2×	6e-03
cytoskeleton organization	5	7.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	24
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

5178 predictions. Top by Δscore:

Variant	Effect	Δscore
16:76280273:GGAT:G	donor_gain	1.0000
16:76316520:GATG:G	donor_gain	1.0000
16:76316521:ATGG:A	donor_loss	1.0000
16:76316523:GGT:G	donor_loss	1.0000
16:76316524:G:C	donor_loss	1.0000
16:76316524:G:GG	donor_gain	1.0000
16:76316525:TAAG:T	donor_loss	1.0000
16:76355305:T:G	acceptor_gain	1.0000
16:76355310:A:AG	acceptor_gain	1.0000
16:76355313:A:AG	acceptor_gain	1.0000
16:76427447:TTTA:T	acceptor_loss	1.0000
16:76427450:A:AG	acceptor_gain	1.0000
16:76427450:AG:A	acceptor_gain	1.0000
16:76427451:G:A	acceptor_gain	1.0000
16:76427451:G:GG	acceptor_gain	1.0000
16:76427451:GGGTT:G	acceptor_gain	1.0000
16:76427596:TACA:T	donor_gain	1.0000
16:76427596:TACAG:T	donor_loss	1.0000
16:76427598:CA:C	donor_gain	1.0000
16:76427598:CAGT:C	donor_loss	1.0000
16:76427599:AG:A	donor_loss	1.0000
16:76427600:G:C	donor_loss	1.0000
16:76427600:G:GG	donor_gain	1.0000
16:76427601:TAAG:T	donor_loss	1.0000
16:76444518:C:G	donor_gain	1.0000
16:76448010:A:AG	acceptor_gain	1.0000
16:76448011:G:GG	acceptor_gain	1.0000
16:76448146:G:T	donor_gain	1.0000
16:76448764:A:AG	acceptor_gain	1.0000
16:76448764:AAG:A	acceptor_gain	1.0000

AlphaMissense

8608 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:76355329:T:A	W70R	0.997
16:76355329:T:C	W70R	0.997
16:76522130:G:C	W876C	0.997
16:76522130:G:T	W876C	0.997
16:76522128:T:A	W876R	0.995
16:76522128:T:C	W876R	0.995
16:76355331:G:C	W70C	0.993
16:76355331:G:T	W70C	0.993
16:76427528:G:C	R156P	0.992
16:76427573:G:C	R171P	0.992
16:76535572:T:G	F928C	0.992
16:76535571:T:C	F928L	0.991
16:76535573:T:A	F928L	0.991
16:76535573:T:G	F928L	0.991
16:76355404:G:C	A95P	0.990
16:76521263:T:C	F830S	0.990
16:76535587:G:C	R933P	0.990
16:76498682:T:A	C785S	0.989
16:76498683:G:C	C785S	0.989
16:76355411:A:C	Q97P	0.988
16:76535572:T:C	F928S	0.988
16:76535694:T:A	C969S	0.988
16:76535695:G:C	C969S	0.988
16:76535775:T:A	C996S	0.988
16:76535776:G:C	C996S	0.988
16:76535777:C:G	C996W	0.988
16:76355481:G:C	W120C	0.987
16:76355481:G:T	W120C	0.987
16:76521164:T:G	F797C	0.987
16:76522131:C:G	H877D	0.987

dbSNP variants (sampled 300 via entrez): RS1000005111 (16:76435420 C>A), RS1000009421 (16:76392498 T>G), RS1000010038 (16:76370307 G>A), RS1000014940 (16:76342109 A>G), RS1000022431 (16:76356270 A>G), RS1000027973 (16:76464824 A>C,T), RS1000028475 (16:76433068 C>T), RS1000045181 (16:76315577 A>G,T), RS1000077707 (16:76315388 G>A), RS1000077711 (16:76309377 G>A), RS1000086173 (16:76376257 A>C,G), RS1000094322 (16:76285621 A>G), RS1000097743 (16:76352220 A>ACC), RS1000109337 (16:76426725 T>C), RS1000112981 (16:76439776 T>C)

Disease associations

OMIM: gene MIM:610518 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001413_5	Sphingolipid levels	2.000000e-08
GCST001510_6	Response to TNF-alpha inhibitors in rheumatoid arthritis	9.000000e-06
GCST001651_64	Response to amphetamines	5.000000e-06
GCST002441_2	Immune response to measles-mumps-rubella vaccine	4.000000e-07
GCST004071_17	Cerebrospinal T-tau levels	9.000000e-06
GCST006298_3	Response to haloperidol in schizophrenia	6.000000e-06
GCST007327_137	Smoking status (ever vs never smokers)	4.000000e-09
GCST007673_6	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06
GCST011154_16	Fasting plasma glucose	5.000000e-06
GCST011348_43	High density lipoprotein cholesterol levels	2.000000e-10
GCST012053_7	Weight	8.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004645	response to vaccine
EFO:0004760	t-tau measurement
EFO:0004318	smoking behavior
EFO:0009603	stroke outcome severity measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004338	body weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6193848 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment	1
belinostat	decreases expression	1
Acetaminophen	decreases expression	1
Calcitriol	increases expression	1
Drugs, Chinese Herbal	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Naphthoquinones	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5037090	Binding	PROTAC activity at CRBN/CNTNAP4 in human MV4-11 cells assessed as induction of CNTNAP4 degradation at 1 uM measured after 4 hrs by tandem mass tag mass spectrometry analysis	Identification of Potent, Selective, and Orally Bioavailable Small-Molecule GSPT1/2 Degraders from a Focused Library of Cereblon Modulators. — J Med Chem

Clinical trials (associated diseases)

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