CFC1B

Summary

CFC1B (cryptic, EGF-CFC family member 1B, HGNC:33983) is a protein-coding gene on chromosome 2q21.1, encoding Cryptic family protein 1B (P0CG36).

Predicted to enable activin receptor binding activity and nodal binding activity. Predicted to be involved in circulatory system development; nodal signaling pathway; and regionalization. Predicted to act upstream of or within several processes, including heart development; left lung morphogenesis; and spleen development. Predicted to be active in cell surface and extracellular region. Implicated in tetralogy of Fallot and visceral heterotaxy.

Source: NCBI Gene 653275 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001079530

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33983
Approved symbol	CFC1B
Name	cryptic, EGF-CFC family member 1B
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000152093
Ensembl biotype	protein_coding
Entrez	653275

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000281882, ENST00000619050, ENST00000620207

RefSeq mRNA: 1 — MANE Select: NM_001079530 NM_001079530

CCDS: CCDS33286

Canonical transcript exons

ENST00000281882 — 6 exons

Exon	Start	End
ENSE00002449422	130522790	130522904
ENSE00002452682	130521957	130522130
ENSE00002480432	130527696	130528603
ENSE00002490771	130523169	130523278
ENSE00002515225	130521813	130521862
ENSE00003847123	130521222	130521507

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 81.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4004 / max 84.4732, expressed in 59 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22515	0.1717	38
202389	0.1368	41
22516	0.0490	29
202390	0.0429	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.22	silver quality
islet of Langerhans	UBERON:0000006	47.85	gold quality
ventricular zone	UBERON:0003053	43.39	gold quality
prefrontal cortex	UBERON:0000451	41.30	gold quality
granulocyte	CL:0000094	41.18	gold quality
rectum	UBERON:0001052	40.29	gold quality
bone marrow cell	CL:0002092	38.29	gold quality
lower esophagus mucosa	UBERON:0035834	37.83	gold quality
right adrenal gland cortex	UBERON:0035827	37.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
apex of heart	UBERON:0002098	36.55	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	36.15	silver quality
sural nerve	UBERON:0015488	35.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.55	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
pancreas	UBERON:0001264	35.28	gold quality
muscle tissue	UBERON:0002385	34.24	gold quality
bone marrow	UBERON:0002371	33.97	gold quality
gall bladder	UBERON:0002110	33.78	gold quality
duodenum	UBERON:0002114	33.59	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
frontal cortex	UBERON:0001870	32.08	gold quality
leukocyte	CL:0000738	31.92	gold quality
superior frontal gyrus	UBERON:0002661	31.88	gold quality
monocyte	CL:0000576	31.56	gold quality
urinary bladder	UBERON:0001255	31.16	silver quality
liver	UBERON:0002107	30.86	gold quality
right adrenal gland	UBERON:0001233	30.84	gold quality
tonsil	UBERON:0002372	30.05	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	2621.68
E-MTAB-9388	yes	530.75
E-HCAD-56	yes	277.52
E-GEOD-83139	yes	10.57
E-ANND-3	yes	4.49
E-HCAD-31	no	30.60
E-MTAB-7303	no	25.70

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cfc1	ENSMUSG00000026124
rattus_norvegicus	Cfc1	ENSRNOG00000042646

Paralogs (5): CFC1 (ENSG00000136698), EGFL7 (ENSG00000172889), CRIPTO3 (ENSG00000225366), CRIPTO (ENSG00000241186), EGFL8 (ENSG00000241404)

Protein

Protein identifiers

Cryptic family protein 1B — P0CG36 (reviewed: P0CG36)

All UniProt accessions (3): P0CG36, A0A087WWE4, A0A087X0G3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.

RefSeq proteins (1): NP_001072998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR019011	Cryptic/Cripto_CFC-dom	Domain

Pfam: PF09443

UniProt features (7 total): disulfide bond 3, signal peptide 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CG36-F1	63.99	0.23

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): 90–97, 91–103, 105–114

Glycosylation sites (1): 52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): GOCC_CELL_SURFACE, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_GASTRULATION, GOBP_ACTIVIN_RECEPTOR_SIGNALING_PATHWAY, GOBP_EMBRYO_DEVELOPMENT, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_MORPHOGENESIS, GOMF_RECEPTOR_SERINE_THREONINE_KINASE_BINDING, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, MIKKELSEN_ES_ICP_WITH_H3K4ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, GOBP_NODAL_SIGNALING_PATHWAY, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY

GO Biological Process (7): blood vessel development (GO:0001568), determination of left/right symmetry (GO:0007368), gastrulation (GO:0007369), heart development (GO:0007507), anterior/posterior pattern specification (GO:0009952), nodal signaling pathway (GO:0038092), signal transduction (GO:0007165)

GO Molecular Function (2): nodal binding (GO:0038100), activin receptor binding (GO:0070697)

GO Cellular Component (2): extracellular region (GO:0005576), cell surface (GO:0009986)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
vasculature development	1
anatomical structure development	1
determination of bilateral symmetry	1
left/right pattern formation	1
ectoderm formation	1
endoderm formation	1
mesoderm formation	1
embryonic morphogenesis	1
animal organ development	1
circulatory system development	1
regionalization	1
activin receptor signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein binding	1
transmembrane receptor protein serine/threonine kinase binding	1

Protein interactions and networks

STRING

356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFC1B	ANKUB1	A6NFN9	507
CFC1B	UPK3BL1	B0FP48	411
CFC1B	MMACHC	Q9Y4U1	369
CFC1B	EVC2	Q86UK5	358
CFC1B	CMTM8	Q8IZV2	318
CFC1B	HEMGN	Q9BXL5	312
CFC1B	MPZL3	Q6UWV2	306
CFC1B	ZSCAN18	Q8TBC5	300
CFC1B	SYT8	Q8NBV8	293
CFC1B	RBP5	P82980	280
CFC1B	EGF	P01133	279
CFC1B	RNF152	Q8N8N0	277
CFC1B	B3GNT7	Q8NFL0	274
CFC1B	ARHGAP42	A6NI28	271
CFC1B	TBX20	Q9UMR3	269

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2A699, A2BD09, A5D7T4, A8MVW0, B0BN44, O77681, O88829, P0CG36, P0CG37, P15907, P51693, P59383, P61132, P70277, P97325, Q03157, Q07105, Q11203, Q3UPI1, Q3UY90, Q5K027, Q5QQ37, Q64685, Q66NC0, Q68BL7, Q6P7B4, Q6UWH4, Q701R2, Q701R3, Q701R4, Q70D51, Q766D5, Q76K27, Q76KP1, Q80WV3, Q866Y3, Q86VZ4, Q8BHP7, Q8CB67, Q8VCS0

Diamond homologs: P0CG36, P0CG37, P13385, P51864, P51865, P97766, Q9I8Q3, O88277, Q5F226, A0A2K5V015, Q5R6R1, Q5T1H1, O97507, Q20911

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

728 predictions. Top by Δscore:

Variant	Effect	Δscore
2:130521508:G:GA	donor_loss	1.0000
2:130521509:T:G	donor_loss	1.0000
2:130521863:G:GG	donor_gain	1.0000
2:130521953:A:AG	acceptor_gain	1.0000
2:130521953:AAAG:A	acceptor_gain	1.0000
2:130521954:AAG:A	acceptor_gain	1.0000
2:130521955:A:AC	acceptor_loss	1.0000
2:130521955:A:AG	acceptor_gain	1.0000
2:130521955:AG:A	acceptor_gain	1.0000
2:130521956:G:A	acceptor_gain	1.0000
2:130521956:G:GG	acceptor_gain	1.0000
2:130521956:GGCT:G	acceptor_gain	1.0000
2:130522127:GAGG:G	donor_gain	1.0000
2:130522129:GG:G	donor_gain	1.0000
2:130522130:GG:G	donor_gain	1.0000
2:130522131:GTAA:G	donor_loss	1.0000
2:130522132:T:A	donor_loss	1.0000
2:130522903:AGGT:A	donor_loss	1.0000
2:130522904:GG:G	donor_loss	1.0000
2:130522905:G:GA	donor_loss	1.0000
2:130521508:G:GG	donor_gain	0.9900
2:130521954:A:G	acceptor_gain	0.9900
2:130521956:GGC:G	acceptor_gain	0.9900
2:130521956:GGCTA:G	acceptor_gain	0.9900
2:130522131:G:GG	donor_gain	0.9900
2:130522789:GGTGC:G	acceptor_gain	0.9900
2:130523167:A:AG	acceptor_gain	0.9900
2:130523168:G:GG	acceptor_gain	0.9900
2:130523168:GT:G	acceptor_gain	0.9900
2:130521503:GTCAG:G	donor_gain	0.9800

AlphaMissense

1437 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:130523199:G:C	W131C	0.994
2:130523199:G:T	W131C	0.994
2:130522846:T:C	F102L	0.992
2:130522848:C:A	F102L	0.992
2:130522848:C:G	F102L	0.992
2:130522868:T:G	F109C	0.991
2:130522847:T:G	F102C	0.990
2:130522867:T:C	F109L	0.990
2:130522869:C:A	F109L	0.990
2:130522869:C:G	F109L	0.990
2:130522883:G:A	C114Y	0.982
2:130522873:G:T	G111C	0.981
2:130522882:T:A	C114S	0.976
2:130522883:G:C	C114S	0.976
2:130522868:T:C	F109S	0.972
2:130522820:A:T	N93I	0.971
2:130522883:G:T	C114F	0.970
2:130522850:G:A	C103Y	0.969
2:130522884:C:G	C114W	0.968
2:130523197:T:A	W131R	0.967
2:130523197:T:C	W131R	0.967
2:130523233:T:C	F143L	0.966
2:130523235:C:A	F143L	0.966
2:130523235:C:G	F143L	0.966
2:130522855:T:A	C105S	0.961
2:130522856:G:C	C105S	0.961
2:130522874:G:T	G111V	0.961
2:130523173:T:A	C123S	0.961
2:130523174:G:C	C123S	0.961
2:130523227:T:A	C141S	0.961

dbSNP variants (sampled 300 via entrez): RS1003875767 (2:130521779 T>A), RS1011692924 (2:130525363 G>C), RS1011806026 (2:130523493 T>C), RS1021829998 (2:130523588 G>A), RS1021839821 (2:130525480 C>CA), RS1023044275 (2:130526207 CACCA>C), RS1029547454 (2:130522516 G>A), RS1035946165 (2:130528939 T>C), RS1036070093 (2:130525711 T>G), RS1040824201 (2:130521797 T>C), RS1041086287 (2:130524439 C>T), RS1048325318 (2:130520787 A>G), RS1048378035 (2:130524177 C>G), RS1049976385 (2:130527557 G>A,C), RS1055994762 (2:130520419 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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