FTCDNL1

Summary

FTCDNL1 (formiminotransferase cyclodeaminase N-terminal like, HGNC:48661) is a protein-coding gene on chromosome 2q33.1, encoding Formiminotransferase N-terminal subdomain-containing protein (E5RQL4).

Predicted to enable folic acid binding activity and transferase activity. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 348751 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001363886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:48661
Approved symbol	FTCDNL1
Name	formiminotransferase cyclodeaminase N-terminal like
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	FONG
Ensembl gene	ENSG00000226124
Ensembl biotype	protein_coding
OMIM	614308
Entrez	348751

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000416668, ENST00000420128, ENST00000420922, ENST00000622774, ENST00000642693, ENST00000703582, ENST00000881260, ENST00000881261, ENST00000881262, ENST00000881263, ENST00000881264

RefSeq mRNA: 4 — MANE Select: NM_001363886 NM_001350853, NM_001350854, NM_001350855, NM_001363886

CCDS: CCDS86906, CCDS86907, CCDS86908, CCDS86909

Canonical transcript exons

ENST00000420128 — 5 exons

Exon	Start	End
ENSE00001653260	199846075	199846170
ENSE00001662091	199819572	199819757
ENSE00001725972	199809272	199812724
ENSE00001790194	199848848	199848969
ENSE00003719114	199850740	199851192

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 83.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2791 / max 52.7256, expressed in 1061 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33154	1.7093	793
33153	1.5698	688

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	83.82	gold quality
muscle of leg	UBERON:0001383	83.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.80	gold quality
right adrenal gland	UBERON:0001233	79.54	gold quality
right adrenal gland cortex	UBERON:0035827	79.35	gold quality
left adrenal gland	UBERON:0001234	78.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.16	gold quality
adrenal tissue	UBERON:0018303	78.14	gold quality
left adrenal gland cortex	UBERON:0035825	77.92	gold quality
adrenal gland	UBERON:0002369	76.21	gold quality
right lobe of liver	UBERON:0001114	76.00	gold quality
adrenal cortex	UBERON:0001235	75.82	gold quality
prefrontal cortex	UBERON:0000451	75.27	gold quality
spinal cord	UBERON:0002240	75.22	gold quality
monocyte	CL:0000576	74.91	gold quality
leukocyte	CL:0000738	74.19	gold quality
left lobe of thyroid gland	UBERON:0001120	72.96	gold quality
anterior cingulate cortex	UBERON:0009835	72.44	gold quality
secondary oocyte	CL:0000655	72.36	silver quality
thyroid gland	UBERON:0002046	72.29	gold quality
nucleus accumbens	UBERON:0001882	71.64	gold quality
putamen	UBERON:0001874	71.23	gold quality
caudate nucleus	UBERON:0001873	70.84	gold quality
islet of Langerhans	UBERON:0000006	70.80	gold quality
right lobe of thyroid gland	UBERON:0001119	70.80	gold quality
liver	UBERON:0002107	70.65	gold quality
right frontal lobe	UBERON:0002810	69.82	gold quality
substantia nigra	UBERON:0002038	69.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.42

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• A single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis, was identified, in a previously unknown gene on chromosome 2q33.1, FONG. (PMID:21573128)
• results suggest that Japanese subjects homozygous for the risk alleles of rs7605378 in FONG and rs12673629 in THSD7A have a significantly higher risk of vertebral fracture (PMID:23303384)
• rs10203122 in FTCDNL1 is associated with a susceptibility to osteoporosis. (PMID:26492493)
• Two genetic variants in the HIBCH and FTCDNL1 genes are associated with susceptibility to developmental dysplasia of the hips among the Han Chinese population of Southwest China. (PMID:39113043)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	ftcdnl1	ENSDARG00000062423

Paralogs (1): FTCD (ENSG00000160282)

Protein

Protein identifiers

Formiminotransferase N-terminal subdomain-containing protein — E5RQL4 (reviewed: E5RQL4)

Alternative names: Formiminotransferase-cyclodeaminase N-terminal-like protein

All UniProt accessions (4): E5RQL4, H3BMM2, H3BRX2, H3BUS8

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Widely expressed with highest levels in liver and skeletal muscle, and moderate levels in kidney, bone and pancreas.

Similarity. Belongs to the formiminotransferase family.

RefSeq proteins (4): NP_001337782, NP_001337783, NP_001337784, NP_001350815* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012886	Formiminotransferase_N	Domain
IPR022384	FormiminoTrfase_cat_dom_sf	Homologous_superfamily
IPR037064	Formiminotransferase_N_sf	Homologous_superfamily
IPR051623	FTCD	Family

Pfam: PF07837

UniProt features (2 total): signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-E5RQL4-F1	76.93	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): GOMF_FOLIC_ACID_BINDING, GOMF_AMIDE_BINDING, GOMF_MODIFIED_AMINO_ACID_BINDING, GOMF_ORGANIC_ACID_BINDING, GOMF_VITAMIN_BINDING, STK33_NOMO_DN, FOXN3_TARGET_GENES, ZNF618_TARGET_GENES, ZSCAN30_TARGET_GENES, MZF1_TARGET_GENES, CUX1_TARGET_GENES, HARALAMBIEVA_PBMC_M_M_R_II_AGE_11_22YO_VACCINATED_VS_UNVACCINATED_7YR_DN, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_24H_ACT_CD4_TCELL_DN, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN, GSE2706_R848_VS_LPS_8H_STIM_DC_UP

GO Biological Process (0):

GO Molecular Function (2): folic acid binding (GO:0005542), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vitamin binding	1
carboxylic acid binding	1
modified amino acid binding	1
heterocyclic compound binding	1
catalytic activity	1

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FTCDNL1	TYW5	A2RUC4	610
FTCDNL1	C2orf69	Q8N8R5	507
FTCDNL1	ZNF823	P16415	477
FTCDNL1	SPATS2L	Q9NUQ6	431
FTCDNL1	MAIP1	Q8WWC4	417
FTCDNL1	MIMS1	Q96ND0	373
FTCDNL1	THOC7	Q6I9Y2	371
FTCDNL1	YAE1	Q9NRH1	348
FTCDNL1	ZSCAN23	Q3MJ62	348
FTCDNL1	IBA57	Q5T440	348
FTCDNL1	YRDC	Q86U90	347
FTCDNL1	NIF3L1	Q9GZT8	336
FTCDNL1	RFTN2	Q52LD8	324
FTCDNL1	DNAI7	Q6TDU7	324
FTCDNL1	METTL5	Q9NRN9	322
FTCDNL1	GTF3C3	Q9Y5Q9	322

IntAct

2 interactions, top by confidence:

A	B	Type	Score
GPC3	PXDNL	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A023PYH0, A6NC05, B5XXW1, B8V7P3, D4AS55, E5RQL4, F5HGC2, O36379, O36380, O36396, O74917, O75663, O98453, P0C733, P0CK47, P0CK48, P0CK56, P0CK57, P15200, P21005, P21071, P21106, P24756, P43151, P54446, P68960, P68961, P92551, Q00058, Q01031, Q196U3, Q1HVB5, Q20A00, Q2V4N5, Q32M92, Q37884, Q495D7, Q66670, Q76ZJ3, Q77374

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1960 predictions. Top by Δscore:

Variant	Effect	Δscore
2:199760833:CCA:C	acceptor_gain	1.0000
2:199760834:CA:C	acceptor_gain	1.0000
2:199760834:CAC:C	acceptor_gain	1.0000
2:199760836:C:CC	acceptor_gain	1.0000
2:199812636:G:C	donor_gain	1.0000
2:199819659:T:TA	donor_gain	1.0000
2:199844378:A:AC	donor_gain	1.0000
2:199844379:C:CC	donor_gain	1.0000
2:199844379:CTT:C	donor_gain	1.0000
2:199844408:TGTGA:T	donor_gain	1.0000
2:199846069:TCTTA:T	donor_loss	1.0000
2:199846070:CTTA:C	donor_loss	1.0000
2:199846071:TTA:T	donor_loss	1.0000
2:199846072:TA:T	donor_loss	1.0000
2:199846073:A:AC	donor_gain	1.0000
2:199846073:AC:A	donor_gain	1.0000
2:199846073:ACCC:A	donor_loss	1.0000
2:199846074:C:CC	donor_gain	1.0000
2:199846074:C:G	donor_loss	1.0000
2:199846074:CC:C	donor_gain	1.0000
2:199846074:CCCAA:C	donor_gain	1.0000
2:199846078:A:C	donor_gain	1.0000
2:199846083:T:C	donor_gain	1.0000
2:199846166:CTTTC:C	acceptor_gain	1.0000
2:199846167:TTTC:T	acceptor_gain	1.0000
2:199846168:TTC:T	acceptor_gain	1.0000
2:199846169:TC:T	acceptor_gain	1.0000
2:199846169:TCC:T	acceptor_loss	1.0000
2:199846170:CC:C	acceptor_gain	1.0000
2:199846171:C:CA	acceptor_loss	1.0000

AlphaMissense

885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:199819642:G:C	F109L	0.965
2:199819642:G:T	F109L	0.965
2:199819644:A:G	F109L	0.965
2:199819711:A:C	F86L	0.961
2:199819711:A:T	F86L	0.961
2:199819713:A:G	F86L	0.961
2:199846133:A:C	F51L	0.956
2:199846133:A:T	F51L	0.956
2:199846135:A:G	F51L	0.956
2:199819660:C:A	R103S	0.954
2:199819660:C:G	R103S	0.954
2:199819705:A:C	F88L	0.928
2:199819705:A:T	F88L	0.928
2:199819707:A:G	F88L	0.928
2:199819661:C:G	R103T	0.918
2:199819647:A:G	W108R	0.909
2:199819647:A:T	W108R	0.909
2:199819663:T:A	R102S	0.897
2:199819663:T:G	R102S	0.897
2:199819717:G:C	S84R	0.876
2:199819717:G:T	S84R	0.876
2:199819719:T:G	S84R	0.876
2:199819657:C:A	K104N	0.868
2:199819657:C:G	K104N	0.868
2:199819643:A:G	F109S	0.852
2:199819645:C:A	W108C	0.851
2:199819645:C:G	W108C	0.851
2:199819661:C:A	R103M	0.850
2:199846104:A:G	I61T	0.842
2:199819712:A:G	F86S	0.837

dbSNP variants (sampled 300 via entrez): RS1000015865 (2:199680573 C>T), RS1000020494 (2:199743693 T>C), RS1000026285 (2:199727223 C>T), RS1000042254 (2:199714185 C>G), RS1000045361 (2:199791667 C>T), RS1000045755 (2:199839947 C>G), RS1000070175 (2:199716902 A>G), RS1000077607 (2:199704392 T>C,G), RS1000096588 (2:199797389 A>G), RS1000137414 (2:199720511 C>T), RS1000148996 (2:199796967 T>C), RS1000183602 (2:199850492 T>C), RS1000190897 (2:199765103 G>A), RS1000197398 (2:199671692 C>A), RS1000211311 (2:199768387 A>C)

Disease associations

OMIM: gene MIM:614308 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001071_1	Osteoporosis	2.000000e-08
GCST002149_16	Schizophrenia	1.000000e-08
GCST004521_125	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004946_83	Schizophrenia	2.000000e-16
GCST006803_6	Schizophrenia	4.000000e-17
GCST007201_274	Schizophrenia	5.000000e-14
GCST007201_36	Schizophrenia	1.000000e-14
GCST008595_64	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-13
GCST010151_6	Carotid intima media thickness x smoking interaction	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
clothianidin	increases expression	1
Benzo(a)pyrene	decreases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Formaldehyde	decreases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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