ZCRB1

Summary

ZCRB1 (zinc finger CCHC-type and RNA binding motif containing 1, HGNC:29620) is a protein-coding gene on chromosome 12q12, encoding Zinc finger CCHC-type and RNA-binding motif-containing protein 1 (Q8TBF4). It is a selective cancer dependency (DepMap: 59.4% of cell lines).

Pre-mRNA splicing is catalyzed by the spliceosome. U12-type spliceosome binds U12-type pre-mRNAs and recognizes the 5’ splice site and branch-point sequence. U11 and U12 snRNPs are components of U12-type spliceosome and function as a molecular bridge connecting both ends of the intron. The protein encoded by this gene contains a RNA recognition motif. It was identified as one of the protein components of U11/U12 snRNPs. This protein and many other U11/U12 snRNP proteins are highly conserved in organisms known to contain U12-type introns. These proteins have been shown to be essential for cell viability, suggesting the key roles in U12-type splicing.

Source: NCBI Gene 85437 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 18 total
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 59.4% of screened cell lines
• MANE Select transcript: NM_033114

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29620
Approved symbol	ZCRB1
Name	zinc finger CCHC-type and RNA binding motif containing 1
Location	12q12
Locus type	gene with protein product
Status	Approved
Aliases	MADP-1, MADP1, RBM36, ZCCHC19, SNRNP31
Ensembl gene	ENSG00000139168
Ensembl biotype	protein_coding
OMIM	610750
Entrez	85437

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000266529, ENST00000548022, ENST00000551102, ENST00000552235, ENST00000552673, ENST00000676501, ENST00000677694, ENST00000678375, ENST00000678390, ENST00000678543, ENST00000679184, ENST00000679269, ENST00000933534

RefSeq mRNA: 1 — MANE Select: NM_033114 NM_033114

CCDS: CCDS8740

Canonical transcript exons

ENST00000266529 — 8 exons

Exon	Start	End
ENSE00000936817	42324019	42324104
ENSE00000936819	42317340	42317447
ENSE00000936820	42313874	42313986
ENSE00001126898	42312086	42313198
ENSE00002424921	42325924	42326094
ENSE00003496232	42317787	42317898
ENSE00003646873	42322418	42322446
ENSE00003789684	42313690	42313765

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.7875 / max 604.8599, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130486	41.5388	1818
130485	0.2487	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	99.21	gold quality
tendon of biceps brachii	UBERON:0008188	99.18	gold quality
globus pallidus	UBERON:0001875	99.09	gold quality
oocyte	CL:0000023	98.97	gold quality
lateral globus pallidus	UBERON:0002476	98.81	gold quality
left ventricle myocardium	UBERON:0006566	98.78	gold quality
tendon	UBERON:0000043	98.76	gold quality
kidney epithelium	UBERON:0004819	98.71	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.56	gold quality
buccal mucosa cell	CL:0002336	98.50	gold quality
calcaneal tendon	UBERON:0003701	98.48	gold quality
upper arm skin	UBERON:0004263	98.46	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.38	gold quality
spinal cord	UBERON:0002240	98.36	gold quality
subthalamic nucleus	UBERON:0001906	98.35	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.12	gold quality
medulla oblongata	UBERON:0001896	98.06	gold quality
inferior vagus X ganglion	UBERON:0005363	98.05	gold quality
pons	UBERON:0000988	98.03	gold quality
substantia nigra pars compacta	UBERON:0001965	97.91	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.89	gold quality
tibialis anterior	UBERON:0001385	97.87	gold quality
myocardium	UBERON:0002349	97.83	gold quality
superior vestibular nucleus	UBERON:0007227	97.81	gold quality
nasal cavity epithelium	UBERON:0005384	97.77	gold quality
ventral tegmental area	UBERON:0002691	97.74	gold quality
substantia nigra	UBERON:0002038	97.73	gold quality
deltoid	UBERON:0001476	97.72	gold quality
midbrain	UBERON:0001891	97.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting ZCRB1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-12129	99.72	67.45	1311

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 59.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• The 5’-flanking region contains an enhancer core motif and binding sites for AP-1, AP-2, and LF-A1. ZCRB1 is characterized by an RNA-binding motif and a CCHC zinc finger motif. (PMID:16959469)
• Using small interfering RNA against MADP1, defective viral RNA synthesis was observed in the knockdown cells, therefore indicating the importance of the protein in coronaviral RNA synthesis. (PMID:22362731)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zcrb1	ENSDARG00000045691
mus_musculus	Zcrb1	ENSMUSG00000022635
rattus_norvegicus	Zcrb1	ENSRNOG00000004996

Paralogs (5): U2AF2 (ENSG00000063244), CSTF2 (ENSG00000101811), RBMX2 (ENSG00000134597), UHMK1 (ENSG00000152332), CSTF2T (ENSG00000177613)

Protein

Protein identifiers

Zinc finger CCHC-type and RNA-binding motif-containing protein 1 — Q8TBF4 (reviewed: Q8TBF4)

Alternative names: U11/U12 small nuclear ribonucleoprotein 31 kDa protein

All UniProt accessions (3): Q8TBF4, F8VXY6, G3V1V1

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome.

Subcellular location. Nucleus. Nucleoplasm.

Induction. Up-regulated by morphine. Down-regulated at 30-36 degrees Celsius while it is up-regulated at 39 degrees Celsius.

RefSeq proteins (1): NP_149105* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR001878	Znf_CCHC	Domain
IPR003954	RRM_euk-type	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034219	ZCRB1_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR044598	ZCRB1	Family

Pfam: PF00076, PF00098

UniProt features (19 total): strand 6, modified residue 3, helix 2, turn 2, chain 1, domain 1, zinc finger region 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2E5H	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBF4-F1	74.41	0.34

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 (3): 155, 210, 216

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-9682706	Replication of the SARS-CoV-1 genome
R-HSA-9694686	Replication of the SARS-CoV-2 genome

MSigDB gene sets: 107 (showing top): chr12q12, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, CREB_Q2_01, REACTOME_MRNA_SPLICING, DODD_NASOPHARYNGEAL_CARCINOMA_UP, ELK1_01, YRTCANNRCGC_UNKNOWN, CETS1P54_01, REACTOME_METABOLISM_OF_RNA, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, SCGGAAGY_ELK1_02, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOCC_U12_TYPE_SPLICEOSOMAL_COMPLEX

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380), mRNA processing (GO:0006397)

GO Molecular Function (5): RNA binding (GO:0003723), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), U12-type spliceosomal complex (GO:0005689), cytosol (GO:0005829), nucleus (GO:0005634), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
SARS-CoV-1 Genome Replication and Transcription	1
SARS-CoV-2 Genome Replication and Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
nuclear lumen	1
spliceosomal complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZCRB1	SNRNP48	Q6IEG0	686
ZCRB1	RNPC3	Q96LT9	684
ZCRB1	SNRNP25	Q9BV90	644
ZCRB1	ZMAT5	Q9UDW3	635
ZCRB1	SNRNP35	Q16560	595
ZCRB1	GXYLT1	Q4G148	583
ZCRB1	TMEM117	Q9H0C3	504
ZCRB1	RBM34	P42696	497
ZCRB1	YEATS4	O95619	460
ZCRB1	RAB14	P35287	460
ZCRB1	AP2A2	O94973	456
ZCRB1	TOP3B	O95985	440
ZCRB1	ANAPC13	Q9BS18	440
ZCRB1	RASAL2	Q9UJF2	434
ZCRB1	WDR54	Q9H977	432

IntAct

98 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
ZCRB1	SF3B1	psi-mi:“MI:0914”(association)	0.640
ZCRB1	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
ZCRB1	PEX1	psi-mi:“MI:0915”(physical association)	0.560
ZCRB1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
ZCRB1	DKC1	psi-mi:“MI:0914”(association)	0.530
ZMAT5	DENND4B	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
SURF2	HEXIM1	psi-mi:“MI:0914”(association)	0.530
ZCRB1	RPSA	psi-mi:“MI:0914”(association)	0.530
ZCRB1		psi-mi:“MI:0915”(physical association)	0.510

BioGRID (210): ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZCRB1 (Affinity Capture-MS), ZRSR2 (Affinity Capture-MS), HIST1H1A (Affinity Capture-MS), PDCD7 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS)

ESM2 similar proteins: A1C646, A1DGS2, A2R7Z2, A4RHN3, A6SGN8, A7EWN6, B0VZS1, B0XS28, B3MSP2, B3MYX2, B3NYY7, B3P935, B4G3E2, B4GUY6, B4I9X1, B4IIC7, B4J4G8, B4JXU2, B4K7S5, B4L710, B4LVR8, B4MA85, B4N1L0, B4NFY1, B4NTY9, B4PP90, B4Q0Y7, B4QS37, C8V330, O43395, Q0CPF9, Q0U6E7, Q1DPD9, Q1HQN4, Q298C0, Q29GU0, Q2H0U6, Q2KIA6, Q2U002, Q499V6

Diamond homologs: A0A0D1C8Z4, A2SW84, A6PVI3, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5DGI7, B5G279, B7P877, C0H859, C0HFE5, C1BY64, O35698, O89086, P19684, P27476, P33240, P52298, P52299, P60824, P60825, P60826, P62995, P62996, P62997, P78795, P98179, Q05AT9, Q08920

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
mRNA Splicing - Minor Pathway	9	32.0×	1e-09
SARS-CoV-2 modulates host translation machinery	9	32.0×	1e-09
Eukaryotic Translation Initiation	5	24.5×	2e-05
Cap-dependent Translation Initiation	5	24.5×	2e-05
SARS-CoV-1 modulates host translation machinery	5	24.5×	2e-05
Eukaryotic Translation Elongation	5	22.1×	2e-05
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	21.6×	3e-05
Influenza Viral RNA Transcription and Replication	6	20.5×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	6	74.1×	2e-08
chromosome condensation	6	55.6×	7e-08
U2-type prespliceosome assembly	8	54.9×	5e-10
cytoplasmic translation	11	22.4×	5e-10
ribosomal small subunit biogenesis	6	15.0×	1e-04
RNA splicing	12	11.6×	5e-08
translation	10	11.3×	1e-06
mRNA splicing, via spliceosome	10	10.1×	4e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

868 predictions. Top by Δscore:

Variant	Effect	Δscore
12:42313195:CTTG:C	acceptor_gain	1.0000
12:42313196:TTG:T	acceptor_gain	1.0000
12:42313197:TG:T	acceptor_gain	1.0000
12:42313198:GCTGT:G	acceptor_loss	1.0000
12:42313199:C:CA	acceptor_loss	1.0000
12:42313199:C:CC	acceptor_gain	1.0000
12:42313200:T:A	acceptor_loss	1.0000
12:42313201:G:C	acceptor_gain	1.0000
12:42313207:C:CT	acceptor_gain	1.0000
12:42313208:A:T	acceptor_gain	1.0000
12:42313684:TAATA:T	donor_loss	1.0000
12:42313685:AATAC:A	donor_loss	1.0000
12:42313686:ATAC:A	donor_loss	1.0000
12:42313687:TAC:T	donor_loss	1.0000
12:42313688:ACCTG:A	donor_loss	1.0000
12:42313689:C:G	donor_loss	1.0000
12:42313762:CTCA:C	acceptor_gain	1.0000
12:42313764:CA:C	acceptor_gain	1.0000
12:42313764:CACT:C	acceptor_gain	1.0000
12:42313766:C:CC	acceptor_gain	1.0000
12:42313767:T:C	acceptor_gain	1.0000
12:42313767:T:TC	acceptor_gain	1.0000
12:42313771:A:AC	acceptor_gain	1.0000
12:42313869:CATA:C	donor_gain	1.0000
12:42313870:ATACA:A	donor_loss	1.0000
12:42313871:TA:T	donor_loss	1.0000
12:42313872:A:AC	donor_gain	1.0000
12:42313872:ACA:A	donor_loss	1.0000
12:42313873:C:CA	donor_gain	1.0000
12:42313873:CA:C	donor_gain	1.0000

AlphaMissense

1453 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:42313938:G:T	R128S	1.000
12:42313960:A:C	C120W	1.000
12:42313961:C:A	C120F	1.000
12:42313961:C:G	C120S	1.000
12:42313961:C:T	C120Y	1.000
12:42313962:A:G	C120R	1.000
12:42313962:A:T	C120S	1.000
12:42313968:A:G	Y118H	1.000
12:42313969:A:C	S117R	1.000
12:42313969:A:T	S117R	1.000
12:42313971:T:G	S117R	1.000
12:42317344:C:G	C110S	1.000
12:42317344:C:T	C110Y	1.000
12:42317345:A:G	C110R	1.000
12:42317345:A:T	C110S	1.000
12:42317352:A:C	C107W	1.000
12:42317353:C:A	C107F	1.000
12:42317353:C:G	C107S	1.000
12:42317353:C:T	C107Y	1.000
12:42317354:A:G	C107R	1.000
12:42317354:A:T	C107S	1.000
12:42317379:C:A	R98S	1.000
12:42317379:C:G	R98S	1.000
12:42317386:A:T	I96N	1.000
12:42317388:G:C	F95L	1.000
12:42317388:G:T	F95L	1.000
12:42317389:A:C	F95C	1.000
12:42317389:A:G	F95S	1.000
12:42317390:A:G	F95L	1.000
12:42317400:T:A	R91S	1.000

dbSNP variants (sampled 300 via entrez): RS1000169360 (12:42316690 T>C), RS1000189452 (12:42319570 C>T), RS1000258868 (12:42311935 A>C), RS1000311313 (12:42311748 A>T), RS1000628681 (12:42324894 A>G), RS1000826428 (12:42319089 G>C), RS1000875295 (12:42316359 C>A), RS1001640636 (12:42326166 T>C), RS1001773968 (12:42313479 G>T), RS1002108059 (12:42321878 C>T), RS1002146166 (12:42314653 G>A), RS1002234631 (12:42327848 A>G), RS1002245036 (12:42315058 C>G,T), RS1002482116 (12:42321415 A>G), RS1002591306 (12:42327658 C>G)

Disease associations

OMIM: gene MIM:610750 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_215	Refractive error	3.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
arsenite	affects binding, increases reaction	1
CGP 52608	affects binding, increases reaction	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Gold	decreases expression	1
Ribonucleotides	affects binding	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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