SNAPC4

Summary

SNAPC4 (small nuclear RNA activating complex polypeptide 4, HGNC:11137) is a protein-coding gene on chromosome 9q34.3, encoding snRNA-activating protein complex subunit 4 (Q5SXM2). Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. It is a common-essential gene (DepMap: required in 98.1% of cancer cell lines).

This gene encodes the largest subunit of the small nuclear RNA-activating protein (SNAP) complex. The encoded protein contains a Myb DNA-binding domain, and is essential for RNA polymerase II and III polymerase transcription from small nuclear RNA promoters. A mutation in this gene is associated with ankylosing spondylitis.

Source: NCBI Gene 6621 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction (Strong, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 411 total — 6 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_003086

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11137
Approved symbol	SNAPC4
Name	small nuclear RNA activating complex polypeptide 4
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	SNAP190, PTFalpha, FLJ13451
Ensembl gene	ENSG00000165684
Ensembl biotype	protein_coding
OMIM	602777
Entrez	6621

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000298532, ENST00000637388, ENST00000682081, ENST00000682698, ENST00000683251, ENST00000684778, ENST00000689006, ENST00000891512, ENST00000891513, ENST00000939539, ENST00000939540, ENST00000939541, ENST00000939542

RefSeq mRNA: 4 — MANE Select: NM_003086 NM_001394201, NM_001394202, NM_001394203, NM_003086

CCDS: CCDS6998

Canonical transcript exons

ENST00000684778 — 24 exons

Exon	Start	End
ENSE00001095441	136381824	136382073
ENSE00001095442	136382253	136382336
ENSE00001095443	136376349	136376481
ENSE00001095444	136396977	136397023
ENSE00001095446	136387742	136387848
ENSE00001095447	136381322	136381392
ENSE00001095448	136383953	136384032
ENSE00001095451	136391942	136392106
ENSE00001095452	136392673	136392777
ENSE00001095453	136392522	136392594
ENSE00001095455	136377543	136379299
ENSE00001095459	136379837	136379864
ENSE00001095462	136395603	136395770
ENSE00001095463	136384720	136384814
ENSE00001095464	136383186	136383668
ENSE00001095465	136388444	136388591
ENSE00001095467	136394800	136394878
ENSE00001095468	136394249	136394330
ENSE00001095470	136395298	136395423
ENSE00001095471	136387485	136387579
ENSE00001095472	136380740	136380850
ENSE00003918263	136400134	136400170
ENSE00003924325	136375571	136375800
ENSE00003926856	136398299	136398437

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 89.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3919 / max 91.4940, expressed in 1697 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103152	6.3919	1697

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	89.11	gold quality
endothelial cell	CL:0000115	86.85	gold quality
right uterine tube	UBERON:0001302	86.43	gold quality
endometrium epithelium	UBERON:0004811	84.81	gold quality
paraflocculus	UBERON:0005351	84.56	gold quality
right testis	UBERON:0004534	84.15	gold quality
left testis	UBERON:0004533	83.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.87	gold quality
frontal pole	UBERON:0002795	83.76	gold quality
diaphragm	UBERON:0001103	83.59	gold quality
cerebellar hemisphere	UBERON:0002245	83.37	gold quality
cerebellar cortex	UBERON:0002129	83.22	gold quality
pancreatic ductal cell	CL:0002079	83.08	silver quality
triceps brachii	UBERON:0001509	82.84	gold quality
nasal cavity epithelium	UBERON:0005384	82.82	silver quality
cerebellum	UBERON:0002037	82.41	gold quality
granulocyte	CL:0000094	82.08	gold quality
sperm	CL:0000019	82.00	silver quality
male germ cell	CL:0000015	81.96	silver quality
testis	UBERON:0000473	81.87	gold quality
middle frontal gyrus	UBERON:0002702	81.85	gold quality
gluteal muscle	UBERON:0002000	81.47	silver quality
epithelium of bronchus	UBERON:0002031	81.11	gold quality
middle temporal gyrus	UBERON:0002771	81.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.79	gold quality
right frontal lobe	UBERON:0002810	80.75	gold quality
type B pancreatic cell	CL:0000169	80.67	gold quality
bronchus	UBERON:0002185	80.60	gold quality
apex of heart	UBERON:0002098	80.57	gold quality
pituitary gland	UBERON:0000007	80.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.56

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
RNU6-1

miRNA regulators (miRDB)

11 targeting SNAPC4, 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-4255	99.72	67.70	1541
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-6872-3P	97.08	66.99	750

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• CK2 may have the capacity to differentially regulate U1 and U6 transcription even though SNAP(C) is universally utilized for human snRNA gene transcription [SNAPC protein, also called PTF or PSE-binding transcription factor] (PMID:15955816)
• CK2 phosphorylation triggers an allosteric inhibition of the SNAP190 Myb DNA binding domain (PMID:17670747)
• Our study confirmed that an SNP rs11145835 in 9q34.3 that harbors CARD9 and SNAPC4 is associated with ankylosing spondylitis in a Chinese Han population (PMID:24334645)
• Report no significant association between SNAPC4 SNPs and ankylosing spondylitis. (PMID:26590821)
• Bi-allelic SNAPC4 variants dysregulate global alternative splicing and lead to neuroregression and progressive spastic paraparesis. (PMID:36965478)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snapc4	ENSDARG00000067673
mus_musculus	Snapc4	ENSMUSG00000036281
rattus_norvegicus	Snapc4	ENSRNOG00000018845
caenorhabditis_elegans	snpc-4	WBGENE00001568

Paralogs (6): CDC5L (ENSG00000096401), MYBL2 (ENSG00000101057), MYB (ENSG00000118513), TTF1 (ENSG00000125482), DMTF1 (ENSG00000135164), MYBL1 (ENSG00000185697)

Protein

Protein identifiers

snRNA-activating protein complex subunit 4 — Q5SXM2 (reviewed: Q5SXM2)

Alternative names: Proximal sequence element-binding transcription factor subunit alpha, snRNA-activating protein complex 190 kDa subunit

All UniProt accessions (3): A0A1B0GUB4, A0A8I5QKS3, Q5SXM2

UniProt curated annotations — full annotation on UniProt →

Function. Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box.

Subunit / interactions. Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC4 interacts with SNAPC1, SNAPC2, SNAPC5, BRF2 and TBP.

Subcellular location. Nucleus.

Disease relevance. Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction (NEDRSO) [MIM:620515] An autosomal recessive disorder characterized by delayed motor development and developmental regression after the first year of life, followed by progressive spasticity with gait alterations, paraparesis, and oromotor dysfunction. Most individuals have cerebral, cerebellar, or basal ganglia volume loss. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (4): NP_001381130, NP_001381131, NP_001381132, NP_003077* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR017930	Myb_dom	Domain
IPR051575	Myb-like_DNA-bd	Family

Pfam: PF13921

UniProt features (98 total): helix 23, region of interest 12, strand 12, compositionally biased region 11, sequence variant 10, modified residue 8, mutagenesis site 8, domain 5, turn 4, DNA-binding region 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
7ZWD	ELECTRON MICROSCOPY	3
7ZX8	ELECTRON MICROSCOPY	3
9K3U	ELECTRON MICROSCOPY	3
7ZWC	ELECTRON MICROSCOPY	3.2
9FSO	ELECTRON MICROSCOPY	3.28
9LXN	ELECTRON MICROSCOPY	3.3
9FSP	ELECTRON MICROSCOPY	3.39
7ZX7	ELECTRON MICROSCOPY	3.4
8IUH	ELECTRON MICROSCOPY	3.4
7XUR	ELECTRON MICROSCOPY	3.49
7ZXE	ELECTRON MICROSCOPY	3.5
9K3V	ELECTRON MICROSCOPY	3.5
9FSQ	ELECTRON MICROSCOPY	3.51
9FSR	ELECTRON MICROSCOPY	3.76
8ITY	ELECTRON MICROSCOPY	3.9
8IUE	ELECTRON MICROSCOPY	4.1
9FSS	ELECTRON MICROSCOPY	4.14
9K3B	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SXM2-F1	53.61	0.11

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 (8): 68, 599, 626, 1157, 1224, 1398, 1400, 1440

Mutagenesis-validated functional residues (8):

Position	Phenotype
94	abolishes snapc5 binding in the absence of snapc1. minimal effect on snapc5 binding in the presence of snapc1.
115	abolishes snapc5 binding in the absence of snapc1. minimal effect on snapc5 binding in the presence of snapc1.
1314	abolishes snapc2-binding.
1355	abolishes snapc2-binding.
1362	abolishes snapc2-binding.
1364	abolishes snapc2-binding.
1369	decreased binding to snapc2.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76071	RNA Polymerase III Transcription Initiation From Type 3 Promoter
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76046	RNA Polymerase III Transcription Initiation

MSigDB gene sets: 106 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, LIAO_METASTASIS, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, MARSON_BOUND_BY_FOXP3_STIMULATED, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GINESTIER_BREAST_CANCER_20Q13_AMPLIFICATION_DN, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_UP, GOBP_SNRNA_TRANSCRIPTION, GOBP_SNRNA_TRANSCRIPTION_BY_RNA_POLYMERASE_III, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP, GOMF_RNA_POLYMERASE_III_GENERAL_TRANSCRIPTION_INITIATION_FACTOR_ACTIVITY, GOMF_RNA_POLYMERASE_III_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (2): snRNA transcription by RNA polymerase II (GO:0042795), snRNA transcription by RNA polymerase III (GO:0042796)

GO Molecular Function (6): RNA polymerase III general transcription initiation factor activity (GO:0000995), RNA polymerase III type 3 promoter sequence-specific DNA binding (GO:0001006), DNA binding (GO:0003677), RNA polymerase II general transcription initiation factor activity (GO:0016251), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), snRNA-activating protein complex (GO:0019185)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RNA Polymerase III Transcription	2
Gene expression (Transcription)	2
RNA Polymerase II Transcription	1
RNA Polymerase III Transcription Initiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
snRNA transcription	2
transcription by RNA polymerase III	2
general transcription initiation factor activity	2
RNA polymerase III cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
transcription regulator complex	1

Protein interactions and networks

STRING

1256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAPC4	SNAPC2	Q13487	997
SNAPC4	SNAPC3	Q92966	997
SNAPC4	SNAPC1	Q16533	996
SNAPC4	SNAPC5	O75971	989
SNAPC4	TAF1A	Q15573	669
SNAPC4	TBP	P20226	660
SNAPC4	PMPCA	Q10713	608
SNAPC4	CARD9	Q9H257	595
SNAPC4	CIMIP5	Q96LR7	583
SNAPC4	POLI	Q9UNA4	516
SNAPC4	SURF6	O75683	490
SNAPC4	AK8	Q96MA6	476
SNAPC4	CAMSAP1	Q5T5Y3	452
SNAPC4	SURF4	O15260	444
SNAPC4	IMMP2L	Q96T52	442

IntAct

60 interactions, top by confidence:

A	B	Type	Score
SNAPC4	SNAPC1	psi-mi:“MI:0914”(association)	0.790
SNAPC1	SNAPC5	psi-mi:“MI:0914”(association)	0.740
SNAPC1	SNAPC5	psi-mi:“MI:0915”(physical association)	0.740
SNAPC4	SNAPC5	psi-mi:“MI:0914”(association)	0.620
SNAPC4	SNAPC5	psi-mi:“MI:0915”(physical association)	0.620
	SNAPC1	psi-mi:“MI:0914”(association)	0.540
	SNAPC1	psi-mi:“MI:0915”(physical association)	0.540
KDM5C	TRIM28	psi-mi:“MI:0914”(association)	0.530
SNAPC4	KDM5C	psi-mi:“MI:0914”(association)	0.530
PHF8	AMPD2	psi-mi:“MI:0914”(association)	0.530
ARFGAP3	SNAPC4	psi-mi:“MI:0915”(physical association)	0.400
SNAPC4	PA	psi-mi:“MI:0915”(physical association)	0.370
SNAPC4	NS	psi-mi:“MI:0915”(physical association)	0.370
NS	SNAPC4	psi-mi:“MI:0915”(physical association)	0.370
NS1	SNAPC4	psi-mi:“MI:0915”(physical association)	0.370
SNAPC4	NS2	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	SNAPC4	psi-mi:“MI:0915”(physical association)	0.370
Cdk1	IFT88	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): SNAPC4 (Affinity Capture-MS), SNAPC4 (Affinity Capture-MS), SNAPC4 (Affinity Capture-MS), SNAPC4 (Affinity Capture-MS), SNAPC4 (Affinity Capture-MS), SNAPC4 (Affinity Capture-MS), SNAPC4 (Reconstituted Complex), SNAPC4 (Synthetic Lethality), SNAPC4 (Co-crystal Structure), SNAPC4 (Affinity Capture-MS), SNAPC4 (Affinity Capture-MS), SNAPC4 (Affinity Capture-MS), SNAPC2 (Reconstituted Complex), SNAPC4 (Reconstituted Complex), POU2F1 (Two-hybrid)

ESM2 similar proteins: A0JNJ4, A2APT9, A6NEL2, A6NP61, B1ASB6, B1WBS3, B2RXF5, F6WEQ6, O15015, O43918, O88282, O88286, O95785, P98168, P98169, Q2M3G4, Q2MHN3, Q2QGD7, Q3U1J1, Q3U381, Q497V6, Q5SW24, Q5SXM2, Q6YND2, Q6ZMQ8, Q6ZMY3, Q7TN08, Q7TSX9, Q80SU3, Q80YE4, Q811H0, Q8BG26, Q8BZW2, Q8C8V1, Q8IX07, Q8IY92, Q8N143, Q8N1G0, Q8NC74, Q8TBE0

Diamond homologs: A0A1U8QIH0, A0A1U8QVN4, A0A6S6AAU0, A2WW87, A7SD85, B0G0Y5, B4FNX4, C8VBH3, E0CJS3, F1B281, F4IRB4, K7UPS5, O04192, O13493, O49608, O49782, O80883, P01103, P01104, P04197, P06876, P0CO94, P10242, P10243, P10244, P20025, P22035, P34127, P39964, P46200, P48972, P51960, P52550, P52551, P81393, P81394, P92948, P9WEF9, Q03237, Q05935

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SNAPC4	“form complex”	SNAPC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	4
Uncertain significance	322
Likely benign	50
Benign	1

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
2580886	NM_003086.4(SNAPC4):c.1157A>G (p.Gln386Arg)	Pathogenic
2580887	NM_003086.4(SNAPC4):c.1321G>A (p.Asp441Asn)	Pathogenic
2580888	NM_003086.4(SNAPC4):c.2428C>T (p.Arg810Ter)	Pathogenic
2580889	NM_003086.4(SNAPC4):c.737+5G>T	Pathogenic
3359237	NM_003086.4(SNAPC4):c.1436T>C (p.Ile479Thr)	Pathogenic
3359238	NM_003086.4(SNAPC4):c.472-2_472-1del	Pathogenic
2580890	NM_003086.4(SNAPC4):c.2527+1G>A	Likely pathogenic
3776084	NM_003086.4(SNAPC4):c.1500+1G>A	Likely pathogenic
4292073	NM_003086.4(SNAPC4):c.810+1G>A	Likely pathogenic
4712290	NM_003086.4(SNAPC4):c.2499+1G>T	Likely pathogenic

SpliceAI

4594 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136376345:TCA:T	donor_loss	1.0000
9:136376347:A:AC	donor_gain	1.0000
9:136376348:C:CC	donor_gain	1.0000
9:136376348:C:CT	donor_loss	1.0000
9:136376348:CCTG:C	donor_gain	1.0000
9:136376478:CTCC:C	acceptor_gain	1.0000
9:136376481:CCTG:C	acceptor_loss	1.0000
9:136376482:C:CC	acceptor_gain	1.0000
9:136376482:CTG:C	acceptor_loss	1.0000
9:136376483:T:A	acceptor_loss	1.0000
9:136379295:GTGGC:G	acceptor_gain	1.0000
9:136379296:TGGC:T	acceptor_gain	1.0000
9:136379297:GGC:G	acceptor_gain	1.0000
9:136379298:GC:G	acceptor_gain	1.0000
9:136379299:CC:C	acceptor_gain	1.0000
9:136379299:CCT:C	acceptor_loss	1.0000
9:136379300:C:CC	acceptor_gain	1.0000
9:136379300:CTGT:C	acceptor_loss	1.0000
9:136383535:T:TA	donor_gain	1.0000
9:136383538:T:TA	donor_gain	1.0000
9:136383669:C:CC	acceptor_gain	1.0000
9:136387575:AACTT:A	acceptor_gain	1.0000
9:136387577:CTT:C	acceptor_gain	1.0000
9:136387578:TT:T	acceptor_gain	1.0000
9:136387579:TCTG:T	acceptor_loss	1.0000
9:136387580:C:CA	acceptor_loss	1.0000
9:136387580:C:CC	acceptor_gain	1.0000
9:136387581:T:A	acceptor_loss	1.0000
9:136387740:A:AC	donor_gain	1.0000
9:136387741:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000074094 (9:136396543 A>G), RS1000346182 (9:136399512 C>A,G), RS1000364525 (9:136401298 C>T), RS1000377403 (9:136383796 C>A,T), RS1000501133 (9:136389367 T>C), RS1000537245 (9:136395123 C>A,T), RS1000825993 (9:136390929 G>A,C), RS1000869701 (9:136386649 G>A), RS1000896585 (9:136383635 C>A), RS1001091340 (9:136391088 C>T), RS1001301927 (9:136376784 C>A,T), RS1001499089 (9:136382478 C>A,T), RS1001539931 (9:136377074 G>A), RS1001727184 (9:136388029 A>T), RS1001735866 (9:136399976 G>A,C)

Disease associations

OMIM: gene MIM:602777 | disease phenotypes: MIM:620515

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction	Strong	Autosomal recessive

Mondo (2): long QT syndrome (MONDO:0002442), neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction (MONDO:0957791)

Orphanet (0):

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001285	Spastic tetraparesis
HP:0001288	Gait disturbance
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0002059	Cerebral atrophy
HP:0002307	Drooling
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0011463	Childhood onset
HP:0033044	Motor regression
HP:0034332	Cognitive regression

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000879_23	Crohn’s disease	1.000000e-36
GCST000964_39	Ulcerative colitis	3.000000e-19
GCST001652_10	Crohn’s disease	4.000000e-06
GCST002726_47	Glucose homeostasis traits	2.000000e-06
GCST004131_21	Inflammatory bowel disease	5.000000e-36
GCST004132_11	Crohn’s disease	6.000000e-30
GCST004133_17	Ulcerative colitis	2.000000e-16
GCST004608_158	Granulocyte percentage of myeloid white cells	4.000000e-13
GCST008643_2	Joint damage in rheumatoid arthritis	1.000000e-06
GCST009391_1482	Metabolite levels	7.000000e-06
GCST011938_3	Takayasu arteritis	2.000000e-06
GCST90002389_357	Lymphocyte percentage of white cells	2.000000e-15
GCST90002399_87	Neutrophil percentage of white cells	5.000000e-19

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006832	disposition index measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0005413	joint damage measurement
EFO:0010414	triacylglycerol 52:2 measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725100 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.82	IC50	150	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178656: Inhibition of SNAPC4 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1500	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression	2
Hydrogen Peroxide	affects expression	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression, affects cotreatment	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
abrine	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
Temozolomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Quercetin	increases expression	1
Ribonucleotides	affects binding	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697386	Binding	Inhibition of SNAPC4 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6K8	SEES3-1V human SNAPC4, clone1	Embryonic stem cell	Male
CVCL_A6K9	SEES3-1V human SNAPC4, clone2	Embryonic stem cell	Male
CVCL_A6L0	SEES3-1V human SNAPC4, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea