FEM1C

Summary

FEM1C (fem-1 homolog C, HGNC:16933) is a protein-coding gene on chromosome 5q22.3, encoding Protein fem-1 homolog C (Q96JP0). Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation.

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in cytosol and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex.

Source: NCBI Gene 56929 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 141 total — 1 likely-pathogenic
• MANE Select transcript: NM_020177

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16933
Approved symbol	FEM1C
Name	fem-1 homolog C
Location	5q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1785, EUROIMAGE686608, EUROIMAGE783647, FEM1A
Ensembl gene	ENSG00000145780
Ensembl biotype	protein_coding
OMIM	608767
Entrez	56929

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000274457, ENST00000855971, ENST00000855972, ENST00000855973, ENST00000855974, ENST00000961938

RefSeq mRNA: 1 — MANE Select: NM_020177 NM_020177

CCDS: CCDS4118

Canonical transcript exons

ENST00000274457 — 3 exons

Exon	Start	End
ENSE00000890230	115542950	115543683
ENSE00001082608	115520908	115525617
ENSE00001277114	115544523	115544775

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 95.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.4454 / max 320.9530, expressed in 1800 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63014	18.2974	1789
63013	3.7287	1583
63009	0.6937	330
63011	0.6093	142
63012	0.1163	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.42	gold quality
male germ cell	CL:0000015	91.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.51	gold quality
amniotic fluid	UBERON:0000173	90.91	gold quality
heart right ventricle	UBERON:0002080	90.87	gold quality
biceps brachii	UBERON:0001507	90.04	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.32	gold quality
ganglionic eminence	UBERON:0004023	89.31	gold quality
ventricular zone	UBERON:0003053	88.59	gold quality
tendon	UBERON:0000043	88.49	gold quality
tendon of biceps brachii	UBERON:0008188	88.42	gold quality
calcaneal tendon	UBERON:0003701	88.39	gold quality
colonic mucosa	UBERON:0000317	88.37	gold quality
medial globus pallidus	UBERON:0002477	88.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.04	gold quality
esophagus squamous epithelium	UBERON:0006920	87.78	gold quality
skeletal muscle tissue	UBERON:0001134	87.43	gold quality
cortical plate	UBERON:0005343	87.34	gold quality
epithelium of esophagus	UBERON:0001976	87.26	gold quality
lower lobe of lung	UBERON:0008949	87.22	gold quality
gastrocnemius	UBERON:0001388	86.90	gold quality
muscle of leg	UBERON:0001383	86.88	gold quality
cauda epididymis	UBERON:0004360	86.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.81	gold quality
muscle organ	UBERON:0001630	86.79	gold quality
muscle tissue	UBERON:0002385	86.49	gold quality
vastus lateralis	UBERON:0001379	86.25	silver quality
left ventricle myocardium	UBERON:0006566	85.92	gold quality
cardiac ventricle	UBERON:0002082	85.91	gold quality
heart left ventricle	UBERON:0002084	85.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.09
E-MTAB-7303	no	127.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

251 targeting FEM1C, 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-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4267	99.96	66.53	2368
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-545-3P	99.95	70.74	2783
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 5)

• The identification of a human homolog of this conserved gene suggests a potential role for this sex-determining molecule in humans. (PMID:11733146)
• FEM1 proteins are ancient regulators of Stem-Loop Binding Protein. (PMID:28118078)
• SENP6 and FEM1C gene expression in liver transplantation predicts transplantation tolerance. (PMID:30720688)
• Molecular basis for arginine C-terminal degron recognition by Cul2(FEM1) E3 ligase. (PMID:33398168)
• Molecular basis for ubiquitin ligase CRL2(FEM1C)-mediated recognition of C-degron. (PMID:33398170)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fem1c	ENSDARG00000102147
mus_musculus	Fem1c	ENSMUSG00000033319
rattus_norvegicus	Fem1c	ENSRNOG00000003578

Paralogs (4): FEM1A (ENSG00000141965), ANKRD33B (ENSG00000164236), ANKRD33 (ENSG00000167612), FEM1B (ENSG00000169018)

Protein

Protein identifiers

Protein fem-1 homolog C — Q96JP0 (reviewed: Q96JP0)

Alternative names: FEM1-gamma

All UniProt accessions (1): Q96JP0

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(FEM1C) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, such as SIL1 or OR51B2, leading to their ubiquitination and degradation. The CRL2(FEM1C) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding. Promotes ubiquitination and degradation of SLBP.

Subunit / interactions. Component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter FEM1C.

Tissue specificity. Widely expressed. Highly expressed in kidney, cardiac tissue, skeletal muscle and testis. Expressed at lower levels in other tissues, including cartilage.

Disease relevance. A dominant de novo FEM1C variant was identified in a patient with neurodevelopmental disorder with absent speech, pyramidal signs, and limb ataxia.

Domain organisation. The first seven ANK repeats at the N-terminus (1-242) are essential for recognition of Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the fem-1 family.

RefSeq proteins (1): NP_064562* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00023, PF12796

UniProt features (62 total): helix 27, mutagenesis site 15, repeat 11, strand 4, sequence variant 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
6XKC	X-RAY DIFFRACTION	2.03
6LF0	X-RAY DIFFRACTION	2.11
6LE6	X-RAY DIFFRACTION	2.33
6LDP	X-RAY DIFFRACTION	2.35
6LEN	X-RAY DIFFRACTION	2.38
6LEY	X-RAY DIFFRACTION	2.39
7JYA	X-RAY DIFFRACTION	2.46
6LBG	X-RAY DIFFRACTION	2.51
6LBN	X-RAY DIFFRACTION	2.9
9UA3	ELECTRON MICROSCOPY	3.28
8Q7R	ELECTRON MICROSCOPY	3.71
8PQL	ELECTRON MICROSCOPY	3.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JP0-F1	94.18	0.88

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 (1): 1

Mutagenesis-validated functional residues (15):

Position	Phenotype
76	strongly reduced binding to c-degron with an arginine at the c-terminus.
77	reduced binding to c-degron with an arginine at the c-terminus. abolished binding to c-degron with an arginine at the c-
117	abolished binding to c-degron with an arginine at the c-terminus.
121	reduced binding to c-degron with an arginine at the c-terminus.
125	strongly reduced binding to c-degron with an arginine at the c-terminus.
126	reduced binding to c-degron with an arginine at the c-terminus. abolished binding to c-degron with an arginine at the c-
148	strongly reduced binding to c-degron with an arginine at the c-terminus.
150	modifies specificity for c-degron at the c-terminus and promotes increased affinity for c-degrons usually recognized by
158	strongly reduced binding to c-degron with an arginine at the c-terminus.
183–191	abolished binding to c-degron with an arginine at the c-terminus.
183–188	modifies specificity for c-degron at the c-terminus and promotes increased affinity for c-degrons usually recognized by
188	reduced binding to c-degron with an arginine at the c-terminus.
188	nearly abolished binding to c-degron with an arginine at the c-terminus.
191	reduced binding to c-degron with an arginine at the c-terminus.
191	strongly reduced binding to c-degron with an arginine at the c-terminus.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 362 (showing top): MODULE_97, GOBP_INFLAMMATORY_RESPONSE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MODULE_182, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, CACCAGC_MIR138, CTATGCA_MIR153, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, TCF4_Q5, DAUER_STAT3_TARGETS_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, CCTGTGA_MIR513, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE

GO Biological Process (3): protein ubiquitination (GO:0016567), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), ubiquitin-dependent protein catabolic process via the C-end degron rule pathway (GO:0140627)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (5): ubiquitin ligase complex (GO:0000151), nucleoplasm (GO:0005654), cytosol (GO:0005829), Cul2-RING ubiquitin ligase complex (GO:0031462), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein modification by small protein conjugation	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
enzyme-substrate adaptor activity	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
nuclear lumen	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FEM1C	CUL2	Q13617	689
FEM1C	DMRT1	Q9Y5R6	505
FEM1C	CUL3	Q13618	479
FEM1C	DCUN1D2	Q6PH85	455
FEM1C	CAPN5	O15484	453
FEM1C	KLHDC3	Q9BQ90	441
FEM1C	MSRB1	Q9NZV6	435
FEM1C	KLHL20	Q9Y2M5	431
FEM1C	KLHDC2	Q9Y2U9	430
FEM1C	RNF123	Q5XPI4	428
FEM1C	APPBP2	Q92624	409
FEM1C	PRAMEF6	Q5VXH4	403
FEM1C	PPM1F	P49593	402
FEM1C	FBXO11	Q86XK2	400
FEM1C	SOX3	P35714	399

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
CUL5	SOCS7	psi-mi:“MI:0914”(association)	0.640
GLMN	FKBP5	psi-mi:“MI:0914”(association)	0.640
FEM1C	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
FEM1C	RPGRIP1	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	FEM1C	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	FEM1C	psi-mi:“MI:0915”(physical association)	0.560
RPGRIP1	FEM1C	psi-mi:“MI:0915”(physical association)	0.560
FEM1C	MALT1	psi-mi:“MI:0915”(physical association)	0.560
FEM1C	CEP63	psi-mi:“MI:0915”(physical association)	0.560
FEM1C	MCM8	psi-mi:“MI:0915”(physical association)	0.560
GLMN	CUL1	psi-mi:“MI:0914”(association)	0.530
DCLK1	DCX	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
CUL2	RNF187	psi-mi:“MI:0914”(association)	0.530
FEM1C	BCL2L11	psi-mi:“MI:0915”(physical association)	0.370
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
TCEAL1	PDCD5	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GPS1	HSPA12A	psi-mi:“MI:0914”(association)	0.350
GLMN	CAND2	psi-mi:“MI:0914”(association)	0.350
FERMT2	FEM1C	psi-mi:“MI:0915”(physical association)	0.000
FEM1C	MALT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): FEM1C (Two-hybrid), RPGRIP1 (Two-hybrid), LZTS2 (Two-hybrid), FEM1C (Affinity Capture-Western), FEM1C (Affinity Capture-MS), FEM1C (Affinity Capture-MS), FEM1C (PCA), FEM1C (Affinity Capture-MS), FEM1C (Two-hybrid), MALT1 (Two-hybrid), CEP63 (Two-hybrid), FEM1C (Affinity Capture-MS), FEM1C (Affinity Capture-MS), FEM1C (Affinity Capture-MS), FEM1C (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A2AGL3, A7MB89, B0LPN4, E9Q401, O60733, P30957, P42694, P49754, P97570, P97819, Q15413, Q29RM5, Q2KIX2, Q2T9K6, Q32PW3, Q3SX45, Q4V890, Q59H18, Q5F361, Q5GIG6, Q5KU39, Q5RF15, Q5U2S6, Q5ZKK2, Q66H07, Q66H63, Q6B858, Q6DFV5, Q6NYU2, Q7T3P8, Q7TQP6, Q8C0T1, Q8CEF1, Q8K0L0, Q8K114, Q8TC84, Q91W86, Q92736

Diamond homologs: A1ZBY1, A7MB89, P0C6P7, Q29RM5, Q2T9K6, Q4V890, Q5ZM55, Q6GPE5, Q6P9Z4, Q7T3P8, Q8C0T1, Q8CEF1, Q96JP0, Q9BSK4, Q9UK73, Q9VFD5, Q9Z2G0, Q9Z2G1, P17221, Q66H07, Q6NLQ8, A0A0R4IQZ2, O43150, Q00653, Q0VC93, Q10728, Q28FJ2, Q3V096, Q4JHE0, Q569N2, Q5U464, Q6JAN1, Q6RI86, Q7SIG6, Q7XUW4, Q7Z713, Q7ZUV0, Q8N9B4, Q94A76, Q96KQ7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
Neddylation	6	15.8×	2e-04
Antigen processing: Ubiquitination & Proteasome degradation	5	10.3×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	6	11.6×	2e-03
protein ubiquitination	6	9.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	132
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2504571	NM_020177.3(FEM1C):c.376G>C (p.Asp126His)	Likely pathogenic

SpliceAI

939 predictions. Top by Δscore:

Variant	Effect	Δscore
5:115525619:T:C	acceptor_gain	1.0000
5:115543679:CCAAA:C	acceptor_gain	1.0000
5:115543680:CAAA:C	acceptor_gain	1.0000
5:115543680:CAAAC:C	acceptor_gain	1.0000
19:4793832:G:GT	donor_gain	0.9900
5:115525614:TTAC:T	acceptor_gain	0.9900
5:115525616:ACCT:A	acceptor_loss	0.9900
5:115525617:CC:C	acceptor_loss	0.9900
5:115525618:C:G	acceptor_loss	0.9900
5:115525619:T:TC	acceptor_gain	0.9900
5:115543681:AAA:A	acceptor_gain	0.9900
5:115543682:AA:A	acceptor_gain	0.9900
5:115543684:C:CC	acceptor_gain	0.9900
5:115544722:C:CA	donor_gain	0.9900
5:115525615:TAC:T	acceptor_gain	0.9800
5:115525617:CCT:C	acceptor_gain	0.9800
5:115525618:C:CC	acceptor_gain	0.9800
5:115543011:ATGT:A	donor_gain	0.9800
5:115543066:T:TA	donor_gain	0.9800
5:115543683:AC:A	acceptor_loss	0.9800
5:115543684:CTAG:C	acceptor_loss	0.9800
5:115543685:T:A	acceptor_loss	0.9800
5:115544525:G:A	donor_gain	0.9800
5:115542827:GACTT:G	donor_loss	0.9700
5:115542828:ACTTA:A	donor_loss	0.9700
5:115542829:CTT:C	donor_loss	0.9700
5:115542830:TTACC:T	donor_loss	0.9700
5:115542831:T:TG	donor_loss	0.9700
5:115542832:A:T	donor_loss	0.9700
5:115542833:C:CA	donor_loss	0.9700

AlphaMissense

4088 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:115524996:A:G	L389P	1.000
5:115525016:G:C	S382R	1.000
5:115525016:G:T	S382R	1.000
5:115525018:T:G	S382R	1.000
5:115525079:C:A	W361C	1.000
5:115525079:C:G	W361C	1.000
5:115525081:A:G	W361R	1.000
5:115525081:A:T	W361R	1.000
5:115525083:A:G	L360P	1.000
5:115525091:G:C	C357W	1.000
5:115525092:C:T	C357Y	1.000
5:115525113:T:A	D350V	1.000
5:115525114:C:G	D350H	1.000
5:115525125:G:T	A346D	1.000
5:115525128:C:A	G345V	1.000
5:115525128:C:T	G345D	1.000
5:115525129:C:A	G345C	1.000
5:115525129:C:G	G345R	1.000
5:115525179:C:G	R328P	1.000
5:115525194:A:G	L323P	1.000
5:115525407:C:T	G252E	1.000
5:115525408:C:G	G252R	1.000
5:115525408:C:T	G252R	1.000
5:115525413:A:G	L250P	1.000
5:115525500:G:T	A221E	1.000
5:115525595:A:C	C189W	1.000
5:115525598:A:C	D188E	1.000
5:115525598:A:T	D188E	1.000
5:115525599:T:A	D188V	1.000
5:115525599:T:C	D188G	1.000

dbSNP variants (sampled 300 via entrez): RS1000053329 (5:115538032 C>A), RS1000125456 (5:115531450 G>A,T), RS1000207561 (5:115521124 A>C,G), RS1000246694 (5:115531645 A>G), RS1000614478 (5:115526643 C>A), RS1000703344 (5:115527182 T>C), RS1000883226 (5:115538226 T>C), RS1000906149 (5:115544573 C>T), RS1000968783 (5:115537771 G>A), RS1001070404 (5:115531929 T>G), RS1001101676 (5:115531745 T>C), RS1001206138 (5:115544768 G>C), RS1001247088 (5:115531027 C>A), RS1001248442 (5:115538542 A>C), RS1001316921 (5:115544746 G>A,C)

Disease associations

OMIM: gene MIM:608767 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004720_2	Conotruncal heart defects (inherited effects)	2.000000e-06
GCST007059_14	Response to antidepressants (symptom improvement)	5.000000e-06
GCST008839_153	Height	6.000000e-11

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
arsenite	affects binding, decreases reaction, increases methylation	2
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
bisphenol A	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
methylparaben	increases expression	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
jinfukang	decreases expression	1
NSC 689534	increases expression, affects binding	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Copper	affects binding, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Formaldehyde	increases expression	1
Phenobarbital	affects expression	1
Phthalic Acids	increases methylation	1
Plant Oils	increases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1X7	HAP1 FEM1C (-) 1	Cancer cell line	Male
CVCL_E1X8	HAP1 FEM1C (-) 2	Cancer cell line	Male
CVCL_E1X9	HAP1 FEM1C (-) 3	Cancer cell line	Male
CVCL_E1XA	HAP1 FEM1C (-) 4	Cancer cell line	Male
CVCL_E1XB	HAP1 FEM1C (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism