CHURC1

Summary

CHURC1 (churchill domain containing 1, HGNC:20099) is a protein-coding gene on chromosome 14q23.3, encoding Protein Churchill (Q8WUH1). Transcriptional activator that mediates FGF signaling during neural development.

Predicted to enable zinc ion binding activity. Predicted to be involved in fibroblast growth factor receptor signaling pathway.

Source: NCBI Gene 91612 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_001386928

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20099
Approved symbol	CHURC1
Name	churchill domain containing 1
Location	14q23.3
Locus type	gene with protein product
Status	Approved
Aliases	My015, FLJ33064
Ensembl gene	ENSG00000258289
Ensembl biotype	protein_coding
OMIM	608577
Entrez	91612

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000547625, ENST00000548752, ENST00000549115, ENST00000551093, ENST00000551947, ENST00000552002, ENST00000556089, ENST00000607599, ENST00000882584, ENST00000927076, ENST00000927077

RefSeq mRNA: 3 — MANE Select: NM_001386928 NM_001204064, NM_001386928, NM_145165

CCDS: CCDS32101, CCDS55921, CCDS55922

Canonical transcript exons

ENST00000549115 — 4 exons

Exon	Start	End
ENSE00003544305	64926010	64926080
ENSE00003574023	64923991	64924126
ENSE00003696566	64914455	64914534
ENSE00003696700	64932138	64935368

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.2178 / max 819.9124, expressed in 1824 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140135	66.2178	1824

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.31	gold quality
left ventricle myocardium	UBERON:0006566	96.77	gold quality
right coronary artery	UBERON:0001625	96.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.56	gold quality
tibial artery	UBERON:0007610	96.41	gold quality
popliteal artery	UBERON:0002250	96.40	gold quality
upper arm skin	UBERON:0004263	96.21	gold quality
left coronary artery	UBERON:0001626	96.17	gold quality
monocyte	CL:0000576	96.07	gold quality
islet of Langerhans	UBERON:0000006	95.94	gold quality
coronary artery	UBERON:0001621	95.92	gold quality
leukocyte	CL:0000738	95.90	gold quality
aorta	UBERON:0000947	95.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.76	gold quality
smooth muscle tissue	UBERON:0001135	95.67	gold quality
descending thoracic aorta	UBERON:0002345	95.56	gold quality
muscle of leg	UBERON:0001383	95.33	gold quality
thoracic aorta	UBERON:0001515	95.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.24	gold quality
ascending aorta	UBERON:0001496	95.24	gold quality
gastrocnemius	UBERON:0001388	95.20	gold quality
skin of hip	UBERON:0001554	95.19	gold quality
endothelial cell	CL:0000115	94.86	gold quality
epithelial cell of pancreas	CL:0000083	94.83	gold quality
superficial temporal artery	UBERON:0001614	94.47	gold quality
visceral pleura	UBERON:0002401	94.47	gold quality
muscle tissue	UBERON:0002385	94.44	gold quality
vermiform appendix	UBERON:0001154	94.41	gold quality
myocardium	UBERON:0002349	94.41	gold quality
parietal pleura	UBERON:0002400	94.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting CHURC1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-186-5P	99.99	70.83	3707
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-5696	99.98	72.36	4487
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 2)

• Embryonic neural inducing factor churchill is not a DNA-binding zinc finger protein: solution structure reveals a solvent-exposed beta-sheet and zinc binuclear cluster (PMID:17610897)
• This is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk. (PMID:21360829)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	churc1	ENSDARG00000010831
mus_musculus	Churc1	ENSMUSG00000090258
rattus_norvegicus	Fntb	ENSRNOG00000007660

Protein

Protein identifiers

Protein Churchill — Q8WUH1 (reviewed: Q8WUH1)

All UniProt accessions (4): B7Z3N2, Q8WUH1, H0YHB4, H0YID9

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that mediates FGF signaling during neural development. Plays a role in the regulation of cell movement. Does not bind DNA by itself.

Similarity. Belongs to the Churchill family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8WUH1-4	4	yes
Q8WUH1-1	1
Q8WUH1-2	2
Q8WUH1-3	3

RefSeq proteins (3): NP_001190993, NP_001373857, NP_660148 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009508	Transcrpt_activator_Churchill	Family
IPR038543	Churchill_sf	Homologous_superfamily

Pfam: PF06573

UniProt features (27 total): binding site 12, strand 7, splice variant 4, turn 3, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2JOX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUH1-F1	93.79	0.85

Functional residue map

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

Ligand- & substrate-binding residues (12): 2; 71; 88; 91; 5; 30; 30; 33; 59; 61; 64; 66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): WANG_LMO4_TARGETS_DN, GOBP_RESPONSE_TO_FIBROBLAST_GROWTH_FACTOR, GOBP_RESPONSE_TO_GROWTH_FACTOR, chr14q23, GOBP_FIBROBLAST_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, ZHENG_BOUND_BY_FOXP3, GOBP_CELL_SURFACE_RECEPTOR_PROTEIN_TYROSINE_KINASE_SIGNALING_PATHWAY, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY, BANP_TARGET_GENES, CBX7_TARGET_GENES, DYRK1A_TARGET_GENES, ELF2_TARGET_GENES, HOXB6_TARGET_GENES, IRF5_TARGET_GENES, ZNF146_TARGET_GENES

GO Biological Process (3): fibroblast growth factor receptor signaling pathway (GO:0008543), positive regulation of DNA-templated transcription (GO:0045893), multicellular organism development (GO:0007275)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
multicellular organismal process	1
anatomical structure development	1
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

710 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHURC1	ZEB2	O60315	797
CHURC1	SERPINA3	P01011	412
CHURC1	PCDH17	O14917	406
CHURC1	FCGBP	Q9Y6R7	404
CHURC1	NPTX2	P47972	396
CHURC1	NPAS4	Q8IUM7	395
CHURC1	HLA-DPA1	P01905	389
CHURC1	C1QC	P02747	383
CHURC1	SIRAL2	Q9NWS6	371
CHURC1	FNTB	P49356	370
CHURC1	CFAP68	Q9H5F2	370
CHURC1	IGF1	P01343	370
CHURC1	PLEKHG3	A1L390	369
CHURC1	CIMAP1D	Q3SX64	355
CHURC1	MRPL43	Q8N983	349

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ARPC4	ARPC1B	psi-mi:“MI:0914”(association)	0.910
ACTR3B	ARPC2	psi-mi:“MI:0914”(association)	0.670
CHURC1	ZNF581	psi-mi:“MI:0915”(physical association)	0.560
CHURC1	ZBTB9	psi-mi:“MI:0915”(physical association)	0.370
SERTAD1	CHURC1	psi-mi:“MI:0915”(physical association)	0.370
ACTR2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
ACTR3B	ARPC2	psi-mi:“MI:0914”(association)	0.350
ACTR2		psi-mi:“MI:0914”(association)	0.350
ARPC3		psi-mi:“MI:0914”(association)	0.350
GOSR1	NBAS	psi-mi:“MI:0914”(association)	0.350
CHURC1	NMT2	psi-mi:“MI:0914”(association)	0.350
CHURC1	ZNF581	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): CHURC1 (Affinity Capture-MS), CHURC1 (Affinity Capture-MS), CHURC1 (Two-hybrid), CHURC1 (Affinity Capture-MS), CHURC1 (Affinity Capture-MS), CHURC1 (Affinity Capture-MS), ARPC3 (Affinity Capture-MS), ACTR2 (Affinity Capture-MS), ARPC1A (Affinity Capture-MS), ARPC5 (Affinity Capture-MS), ACTR3 (Affinity Capture-MS), CHURC1 (Affinity Capture-MS), ACTR3B (Affinity Capture-MS), UBB (Affinity Capture-MS), GLRX (Affinity Capture-MS)

ESM2 similar proteins: A0L3X0, A0RMQ6, A1SYJ9, A1VAL0, A1VXN9, A4XJM8, A5G8U0, A5ILC5, A5N3K1, A6Q6S1, A8FJW4, A9BJ07, B0K1F3, B0K7H0, B0S2B9, B2TJY1, B2UZI1, B8DRV3, B8FEA3, B8FZ78, B8GPB9, B9DX85, B9MR65, C0H406, C0H410, O31798, O48425, O54311, P03769, P9WK08, P9WK09, Q24ML8, Q2HJG7, Q30P97, Q30X20, Q38490, Q3A127, Q3IJB4, Q5HX10, Q5R6Q5

Diamond homologs: Q2HJG7, Q5R6Q5, Q5U3N7, Q66JD9, Q6DG52, Q8WUH1, Q9DFZ3, Q9DFZ4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 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.

GO biological processes:

GO term	Partners	Fold	FDR
Arp2/3 complex-mediated actin nucleation	5	438.9×	1e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1036 predictions. Top by Δscore:

Variant	Effect	Δscore
14:64923989:A:AG	acceptor_gain	1.0000
14:64923989:AG:A	acceptor_gain	1.0000
14:64923990:G:A	acceptor_gain	1.0000
14:64923990:G:GG	acceptor_gain	1.0000
14:64923990:GGGT:G	acceptor_gain	1.0000
14:64923990:GGGTA:G	acceptor_gain	1.0000
14:64924122:TGATC:T	donor_gain	1.0000
14:64924123:GATC:G	donor_gain	1.0000
14:64924123:GATCG:G	donor_gain	1.0000
14:64924124:ATC:A	donor_gain	1.0000
14:64924125:TC:T	donor_gain	1.0000
14:64924126:CG:C	donor_loss	1.0000
14:64924127:G:A	donor_loss	1.0000
14:64924127:G:GG	donor_gain	1.0000
14:64924128:TAA:T	donor_loss	1.0000
14:64930875:G:GT	donor_gain	1.0000
14:64939834:TTCTC:T	acceptor_gain	1.0000
14:64939836:CTC:C	acceptor_gain	1.0000
14:64939838:CCTAG:C	acceptor_loss	1.0000
14:64939839:C:CC	acceptor_gain	1.0000
14:64939840:T:G	acceptor_loss	1.0000
14:64942499:CCTCA:C	donor_loss	1.0000
14:64942500:CTCA:C	donor_loss	1.0000
14:64942501:TCAC:T	donor_loss	1.0000
14:64942502:CA:C	donor_loss	1.0000
14:64942503:ACCTG:A	donor_loss	1.0000
14:64942504:CCTGA:C	donor_loss	1.0000
14:64914533:GG:G	donor_gain	0.9900
14:64914534:GG:G	donor_gain	0.9900
14:64914535:G:GG	donor_gain	0.9900

AlphaMissense

926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:64924039:T:C	C57R	0.999
14:64926015:T:C	C88R	0.999
14:64926057:T:C	F102L	0.999
14:64926059:C:A	F102L	0.999
14:64926059:C:G	F102L	0.999
14:64932153:T:C	C115R	0.999
14:64932155:T:G	C115W	0.999
14:64932162:T:C	C118R	0.999
14:64932163:G:A	C118Y	0.999
14:64932164:C:G	C118W	0.999
14:64932165:G:C	G119R	0.999
14:64932166:G:A	G119D	0.999
14:64924029:C:A	N53K	0.998
14:64924029:C:G	N53K	0.998
14:64924039:T:A	C57S	0.998
14:64924040:G:C	C57S	0.998
14:64924048:T:C	C60R	0.998
14:64926015:T:A	C88S	0.998
14:64926016:G:C	C88S	0.998
14:64926017:T:G	C88W	0.998
14:64926039:G:C	A96P	0.998
14:64926040:C:A	A96D	0.998
14:64926045:C:G	H98D	0.998
14:64932154:G:A	C115Y	0.998
14:64932160:T:C	L117S	0.998
14:64932162:T:A	C118S	0.998
14:64932163:G:C	C118S	0.998
14:64932163:G:T	C118F	0.998
14:64932165:G:T	G119C	0.998
14:64932166:G:T	G119V	0.998

dbSNP variants (sampled 300 via entrez): RS1000405287 (14:64914216 C>T), RS1000469258 (14:64922533 G>A), RS1000488309 (14:64925833 G>A,T), RS1000641784 (14:64931629 A>G), RS1000837619 (14:64926142 C>A,G), RS1001099578 (14:64916805 C>T), RS1001254721 (14:64928897 A>G,T), RS1001441949 (14:64928760 C>G,T), RS1001459828 (14:64914870 A>G,T), RS1001566166 (14:64928287 G>A,T), RS1001863267 (14:64928180 G>A,T), RS1001899570 (14:64918400 C>G), RS1002089957 (14:64921994 G>A,C), RS1002111616 (14:64924863 T>C), RS1002258761 (14:64930199 C>G,T)

Disease associations

OMIM: gene MIM:608577 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003518_66	Daytime sleep phenotypes	4.000000e-06
GCST004862_27	Itch intensity from mosquito bite adjusted by bite size	6.000000e-07
GCST90002397_360	Mean spheric corpuscular volume	6.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4902333	Efficacy	3	methylphenidate	Attention Deficit Disorder with Hyperactivity

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Cocaine	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
uranyl acetate	increases expression	1
methylparaben	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Heroin	decreases expression	1
Smoke	decreases expression	1
Uranium	increases expression	1
Urethane	decreases expression	1
Sodium Selenite	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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