RFX7

Summary

RFX7 (regulatory factor X7, HGNC:25777) is a protein-coding gene on chromosome 15q21.3, encoding DNA-binding protein RFX7 (Q2KHR2). Transcription factor.

RFX7 is a member of the regulatory factor X (RFX) family of transcription factors (see RFX1, MIM 600006) (Aftab et al., 2008 [PubMed 18673564]).

Source: NCBI Gene 64864 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 359 total — 5 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 75
• MANE Select transcript: NM_022841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25777
Approved symbol	RFX7
Name	regulatory factor X7
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12994
Ensembl gene	ENSG00000181827
Ensembl biotype	protein_coding
OMIM	612660
Entrez	64864

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 nonsense_mediated_decay

ENST00000559447, ENST00000559847, ENST00000560792, ENST00000673948, ENST00000673997, ENST00000674082, ENST00000910208, ENST00000917784, ENST00000917785, ENST00000917786, ENST00000917787, ENST00000917788

RefSeq mRNA: 5 — MANE Select: NM_022841 NM_001368073, NM_001368074, NM_001370554, NM_001370561, NM_022841

CCDS: CCDS92003, CCDS92004, CCDS92005

Canonical transcript exons

ENST00000559447 — 10 exons

Exon	Start	End
ENSE00001367933	56101359	56101566
ENSE00001386445	56098081	56098376
ENSE00002539499	56243125	56243287
ENSE00002549465	56087280	56096620
ENSE00003896291	56144401	56144483
ENSE00003897160	56243445	56243879
ENSE00003897487	56179270	56179303
ENSE00003897524	56142778	56142900
ENSE00003897605	56103554	56103670
ENSE00003897805	56102169	56102253

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 92.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4688 / max 214.2875, expressed in 1785 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150159	8.2347	1721
150155	1.6221	725
150158	1.6130	917
150165	1.3500	705
150156	0.7384	405
150162	0.5103	282
150157	0.4910	250
150160	0.2374	76
150161	0.1916	46
150164	0.1720	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.49	gold quality
cortical plate	UBERON:0005343	90.93	gold quality
upper leg skin	UBERON:0004262	90.59	gold quality
ganglionic eminence	UBERON:0004023	89.77	gold quality
ventricular zone	UBERON:0003053	89.26	gold quality
biceps brachii	UBERON:0001507	89.19	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.49	gold quality
germinal epithelium of ovary	UBERON:0001304	88.36	gold quality
buccal mucosa cell	CL:0002336	88.17	gold quality
skin of hip	UBERON:0001554	87.65	gold quality
endothelial cell	CL:0000115	87.64	gold quality
mammary duct	UBERON:0001765	87.44	gold quality
visceral pleura	UBERON:0002401	87.03	gold quality
parietal pleura	UBERON:0002400	87.00	gold quality
tibia	UBERON:0000979	86.43	gold quality
gingival epithelium	UBERON:0001949	86.31	gold quality
pleura	UBERON:0000977	85.61	gold quality
penis	UBERON:0000989	85.53	gold quality
caput epididymis	UBERON:0004358	85.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.78	gold quality
gingiva	UBERON:0001828	84.66	gold quality
superior surface of tongue	UBERON:0007371	84.29	gold quality
corpus epididymis	UBERON:0004359	83.95	gold quality
epithelium of mammary gland	UBERON:0003244	83.94	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.90	gold quality
jejunum	UBERON:0002115	83.85	gold quality
oral cavity	UBERON:0000167	83.62	gold quality
epithelium of nasopharynx	UBERON:0001951	83.32	gold quality
lower lobe of lung	UBERON:0008949	83.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

325 targeting RFX7, 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-3163	100.00	77.23	8605
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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3185	99.99	68.12	1959

Literature-anchored findings (GeneRIF, showing 3)

• RFX7 is a winged helix transcription factor expressed ubiquitously in all tissues examined, especially brain tissue. (PMID:18673564)
• Structural basis for the recognition of RFX7 by ANKRA2 and RFXANK. (PMID:31864703)
• Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress. (PMID:34197623)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rfx7a	ENSDARG00000077237
danio_rerio	rfx7b	ENSDARG00000103691
mus_musculus	Rfx7	ENSMUSG00000037674
rattus_norvegicus	Rfx7	ENSRNOG00000060367
drosophila_melanogaster	CG9727	FBGN0037445

Paralogs (7): RFX3 (ENSG00000080298), RFX2 (ENSG00000087903), RFX4 (ENSG00000111783), RFX1 (ENSG00000132005), RFX5 (ENSG00000143390), RFX6 (ENSG00000185002), RFX8 (ENSG00000196460)

Protein

Protein identifiers

DNA-binding protein RFX7 — Q2KHR2 (reviewed: Q2KHR2)

Alternative names: Regulatory factor X 7, Regulatory factor X domain-containing protein 2

All UniProt accessions (5): Q2KHR2, A0A8C8UYX0, A0AAA9Y9D9, H0YLX2, H0YMH6

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Acts as a transcriptional activator by binding to promoter regions of target genes, such as PDCD4, PIK3IP1, MXD4, PNRC1, and RFX5. Plays a role in natural killer (NK) cell maintenance and immunity. May play a role in the process of ciliogenesis in the neural tube and neural tube closure.

Subunit / interactions. Interacts (via PxLPxI/L motif) with RFXANK (via ankyrin repeats). Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats).

Subcellular location. Nucleus.

Tissue specificity. Widely expressed in many different tissue types including thymus and placenta, with high expression in brain. Expressed in both inhibitory and excitatory neurons in cortex.

Disease relevance. Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities (MRD71) [MIM:620330] An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, hypotonia, speech delay, and impaired intellectual development. Most patients manifest neurobehavioral features including autism spectrum disorder and attention-deficit/hyperactivity disorder. Other frequent features include hypersensitivity to sensory stimuli and sleep problems. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2 and RFXANK.

Similarity. Belongs to the RFX family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2KHR2-3	1	yes
Q2KHR2-1	3
Q2KHR2-2	2

RefSeq proteins (5): NP_001355002, NP_001355003, NP_001357483, NP_001357490, NP_073752* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003150	DNA-bd_RFX	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR039779	RFX-like	Family

Pfam: PF02257, PF18326

UniProt features (46 total): compositionally biased region 11, sequence variant 11, modified residue 10, region of interest 6, sequence conflict 3, splice variant 2, chain 1, DNA-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6MEW	X-RAY DIFFRACTION	1.78
4QQI	X-RAY DIFFRACTION	2.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2KHR2-F1	43.61	0.10

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 (10): 322, 379, 418, 455, 564, 662, 704, 988, 1178, 1329

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 405 (showing top): SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GFI1_01, MODULE_48, MODULE_95, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, MARIADASON_RESPONSE_TO_BUTYRATE_SULINDAC_6, MCCABE_HOXC6_TARGETS_UP, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, MODULE_69, PASQUALUCCI_LYMPHOMA_BY_GC_STAGE_DN, GOMF_RNA_POLYMERASE_II_CORE_PROMOTER_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_CORE_PROMOTER_SEQUENCE_SPECIFIC_DNA_BINDING, EPPERT_PROGENITOR, WANG_METASTASIS_OF_BREAST_CANCER

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	2
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
core promoter sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFX7	RFX8	Q6ZV50	606
RFX7	RFX4	Q33E94	533
RFX7	RFX1	P22670	523
RFX7	RFX6	Q8HWS3	494
RFX7	RFX2	P48378	492
RFX7	TM7SF3	Q9NS93	456
RFX7	ODAD4	Q96NG3	455
RFX7	RFX3	P48380	450
RFX7	CCNK	O75909	440
RFX7	SS18L1	O75177	437
RFX7	PRRG3	Q9BZD7	432
RFX7	RFX5	P48382	431
RFX7	DDX1	Q92499	414
RFX7	DTX1	Q86Y01	413
RFX7	TMEM179B	Q7Z7N9	398

IntAct

32 interactions, top by confidence:

A	B	Type	Score
RFX5	RFXAP	psi-mi:“MI:0914”(association)	0.880
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
RFXANK	RFX7	psi-mi:“MI:0407”(direct interaction)	0.760
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
ANKRA2	RFX7	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
OTUB1		psi-mi:“MI:0914”(association)	0.350
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
ANKRA2	RFXAP	psi-mi:“MI:0914”(association)	0.350
RFXANK	BLTP3B	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPK3	HMMR	psi-mi:“MI:0914”(association)	0.350
DYRK1B	POM121C	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NFYC	ASDURF	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (33): RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), ANKRA2 (Reconstituted Complex), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-RNA), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), RFX7 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IYX6, A0A1L8H0H2, A5X7A0, A7XYJ6, E1BE02, F6NSX9, F8VPJ6, O35914, O57415, P37275, P59598, P59759, Q03172, Q13029, Q2KHR2, Q3UH06, Q5EXX3, Q5R7F2, Q5ZIE8, Q5ZLR2, Q62947, Q63755, Q64318, Q6NRM0, Q6ZPY7, Q76L83, Q7LBC6, Q7YR76, Q80VX4, Q86V15, Q8BHZ4, Q8BLG0, Q8BRH4, Q8BX22, Q8BZ32, Q8C0C0, Q8IZQ8, Q8NEZ4, Q8R5I7, Q8VIM5

Diamond homologs: A0A1L8GWK2, A0A1L8H0H2, A0JMF8, A2BGA0, A6QLW9, B1WAV2, B2GV50, D2HNW6, F8VPJ6, P22670, P48377, P48378, P48379, P48380, P48381, P48382, P48743, Q09555, Q0V9K5, Q2KHR2, Q32NR3, Q33E94, Q4R3I8, Q4R3Z4, Q59V88, Q5EAP5, Q5RDR2, Q5RJA1, Q7TNK1, Q8C7R7, Q8HWS3, Q9JL61, D3YU81, P48383, Q6ZV50, Q5AMQ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	176.8×	7e-09
RHO GTPases activate PKNs	5	83.5×	2e-07
Intrinsic Pathway for Apoptosis	5	77.1×	3e-07
Apoptosis	5	44.2×	3e-06
Programmed Cell Death	5	38.5×	5e-06
RHO GTPase Effectors	5	17.9×	1e-04
Signaling by Rho GTPases	6	10.8×	2e-04
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	6	10.6×	2e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	10
Uncertain significance	248
Likely benign	75
Benign	8

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1313255	NM_022841.7(RFX7):c.2468T>G (p.Leu823Ter)	Pathogenic
1712559	NM_022841.7(RFX7):c.3083C>T (p.Pro1028Leu)	Pathogenic
2499502	NM_022841.7(RFX7):c.3032del (p.Ser1011fs)	Pathogenic
2499503	NM_022841.7(RFX7):c.2718C>A (p.Tyr906Ter)	Pathogenic
3376854	NM_022841.7(RFX7):c.1399_1400del (p.Met467fs)	Pathogenic
2458588	NM_022841.7(RFX7):c.2233G>T (p.Glu745Ter)	Likely pathogenic
2578396	NM_022841.7(RFX7):c.2116_2117del (p.Glu706fs)	Likely pathogenic
2629767	NM_022841.7(RFX7):c.2052del (p.Thr684_Ile685insTer)	Likely pathogenic
3432641	NM_022841.7(RFX7):c.2833_2839dup (p.Thr947fs)	Likely pathogenic
3897629	NM_022841.7(RFX7):c.1464del (p.Lys490fs)	Likely pathogenic
4076373	NM_022841.7(RFX7):c.100dup (p.Val34fs)	Likely pathogenic
4076377	NM_022841.7(RFX7):c.45_55del (p.His16fs)	Likely pathogenic
4689840	NM_022841.7(RFX7):c.1287C>A (p.Tyr429Ter)	Likely pathogenic
4819144	NM_022841.7(RFX7):c.2680_2681dup (p.Met894fs)	Likely pathogenic
4845504	NM_022841.7(RFX7):c.2236C>T (p.Gln746Ter)	Likely pathogenic

SpliceAI

3013 predictions. Top by Δscore:

Variant	Effect	Δscore
15:56098147:T:TA	donor_gain	1.0000
15:56098169:C:CA	donor_gain	1.0000
15:56098377:C:CC	acceptor_gain	1.0000
15:56098378:T:G	acceptor_loss	1.0000
15:56101562:TCCAA:T	acceptor_gain	1.0000
15:56101563:CCAA:C	acceptor_gain	1.0000
15:56101563:CCAAC:C	acceptor_gain	1.0000
15:56101564:CAA:C	acceptor_gain	1.0000
15:56101564:CAAC:C	acceptor_gain	1.0000
15:56101565:AA:A	acceptor_gain	1.0000
15:56101566:ACT:A	acceptor_loss	1.0000
15:56101566:ACTAG:A	acceptor_gain	1.0000
15:56101567:C:CC	acceptor_gain	1.0000
15:56101567:CT:C	acceptor_loss	1.0000
15:56101568:T:C	acceptor_loss	1.0000
15:56102242:C:CC	acceptor_gain	1.0000
15:56102252:A:C	acceptor_gain	1.0000
15:56103533:CA:C	donor_gain	1.0000
15:56142770:CTA:C	donor_gain	1.0000
15:56142773:CT:C	donor_loss	1.0000
15:56142774:TT:T	donor_loss	1.0000
15:56142775:TA:T	donor_loss	1.0000
15:56142776:A:AC	donor_gain	1.0000
15:56142776:ACTTG:A	donor_loss	1.0000
15:56142777:C:CA	donor_gain	1.0000
15:56142777:CT:C	donor_gain	1.0000
15:56142777:CTTGT:C	donor_gain	1.0000
15:56142796:T:TA	donor_gain	1.0000
15:56142797:C:A	donor_gain	1.0000
15:56142897:ATCA:A	acceptor_gain	1.0000

AlphaMissense

9652 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:56095056:A:G	L794P	1.000
15:56101485:A:G	W132R	1.000
15:56101485:A:T	W132R	1.000
15:56102236:A:G	L82P	1.000
15:56102239:C:T	G81E	1.000
15:56102251:T:C	Y77C	1.000
15:56103552:A:G	Y77H	1.000
15:56103557:G:A	S75F	1.000
15:56103563:C:T	G73D	1.000
15:56103564:C:G	G73R	1.000
15:56103566:C:A	R72I	1.000
15:56103572:C:A	G70V	1.000
15:56103572:C:T	G70D	1.000
15:56103573:C:A	G70C	1.000
15:56103573:C:G	G70R	1.000
15:56103575:A:G	L69S	1.000
15:56103579:G:A	R68C	1.000
15:56103579:G:C	R68G	1.000
15:56103579:G:T	R68S	1.000
15:56103582:G:T	R67S	1.000
15:56103598:A:C	F61L	1.000
15:56103598:A:T	F61L	1.000
15:56103599:A:G	F61S	1.000
15:56103600:A:C	F61V	1.000
15:56103600:A:G	F61L	1.000
15:56103607:T:A	K58N	1.000
15:56103607:T:G	K58N	1.000
15:56103608:T:A	K58I	1.000
15:56103609:T:C	K58E	1.000
15:56103611:A:C	M57R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006164 (15:56184815 G>C), RS1000008522 (15:56181996 T>A,G), RS1000013800 (15:56157023 C>T), RS1000027597 (15:56161808 A>C), RS1000059490 (15:56181802 T>C), RS1000068921 (15:56116894 G>C), RS1000137299 (15:56115705 G>C), RS1000155514 (15:56109094 G>A,C), RS1000216704 (15:56188557 A>G), RS1000234321 (15:56111753 G>A,C,T), RS1000256551 (15:56128945 C>T), RS1000326641 (15:56232890 C>T), RS1000368557 (15:56194211 T>C), RS1000419524 (15:56193899 A>C), RS1000456917 (15:56238389 A>G)

Disease associations

OMIM: gene MIM:612660 | disease phenotypes: MIM:620330

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (3): intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities (MONDO:0957228), microcephaly (MONDO:0001149), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000046	Small scrotum
HP:0000126	Hydronephrosis
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000275	Narrow face
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000324	Facial asymmetry
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000470	Short neck
HP:0000506	Telecanthus
HP:0000582	Upslanted palpebral fissure
HP:0000609	Optic nerve hypoplasia
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000712	Emotional lability
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002073_19	Chronic lymphocytic leukemia	2.000000e-13
GCST002299_17	Chronic lymphocytic leukemia	4.000000e-07
GCST002595_8	Clozapine-induced agranulocytosis	9.000000e-07
GCST002782_116	Waist-to-hip ratio adjusted for body mass index	9.000000e-09
GCST002782_117	Waist-to-hip ratio adjusted for body mass index	4.000000e-06
GCST002782_118	Waist-to-hip ratio adjusted for body mass index	2.000000e-09
GCST003468_15	Chronic lymphocytic leukemia	2.000000e-13
GCST004146_37	Chronic lymphocytic leukemia	2.000000e-18
GCST004508_22	Waist-to-hip ratio adjusted for BMI in non-smokers	7.000000e-06
GCST006085_62	Prostate cancer	1.000000e-08
GCST009201_13	Sub-cortical grey matter volume	6.000000e-06
GCST009264_15	Thalamus volume	2.000000e-06
GCST90020024_484	A body shape index	6.000000e-15
GCST90020024_486	A body shape index	3.000000e-14
GCST90020029_292	Waist circumference adjusted for body mass index	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0005420	grey matter volume measurement
EFO:0006935	thalamus volume
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
trichostatin A	affects cotreatment, decreases expression, affects expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Formaldehyde	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Estradiol	affects expression	1

Clinical trials (associated diseases)

219 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
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.
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