PRR12

Summary

PRR12 (proline rich 12, HGNC:29217) is a protein-coding gene on chromosome 19q13.33, encoding Proline-rich protein 12 (Q9ULL5). May play a role in the regulation of cohesin complex loading onto chromatin, probably acting in coordination with NIPBL and MAU2. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a proline-rich protein that contains two A-T hook DNA binding domains. A chromosomal translocation and gene fusion between this gene and zinc finger, MIZ-type containing 1 (Gene ID: 57178) may underlie intellectual disability and neuropsychiatric problems in a human patient. Enriched expression of this gene in embryonic mouse brain suggests that this gene may play a role in nervous system development.

Source: NCBI Gene 57479 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuroocular syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 759 total — 47 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 75
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_020719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29217
Approved symbol	PRR12
Name	proline rich 12
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000126464
Ensembl biotype	protein_coding
OMIM	616633
Entrez	57479

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000418929, ENST00000593853

RefSeq mRNA: 1 — MANE Select: NM_020719 NM_020719

CCDS: CCDS46143

Canonical transcript exons

ENST00000418929 — 14 exons

Exon	Start	End
ENSE00000720857	49599272	49599938
ENSE00000720861	49601491	49601918
ENSE00000720869	49614533	49614649
ENSE00000720872	49614876	49615009
ENSE00000720874	49615747	49616219
ENSE00000720876	49620352	49620477
ENSE00000720879	49621525	49621622
ENSE00000720881	49624844	49624990
ENSE00000720883	49625105	49625200
ENSE00001425807	49625461	49626439
ENSE00001650300	49591182	49591740
ENSE00001696997	49594454	49594615
ENSE00001761055	49594697	49598013
ENSE00001795027	49593327	49593439

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 91.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.1261 / max 283.5420, expressed in 1801 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177027	27.9923	1799
177029	3.2202	1179
177028	1.0622	668
177031	0.6388	323
177026	0.2126	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	91.48	silver quality
cardia of stomach	UBERON:0001162	91.14	gold quality
nipple	UBERON:0002030	91.05	gold quality
ventral tegmental area	UBERON:0002691	90.82	gold quality
vena cava	UBERON:0004087	90.23	silver quality
right hemisphere of cerebellum	UBERON:0014890	89.38	gold quality
pylorus	UBERON:0001166	89.31	gold quality
cerebellar vermis	UBERON:0004720	89.15	silver quality
renal medulla	UBERON:0000362	89.08	gold quality
cortical plate	UBERON:0005343	88.95	gold quality
sural nerve	UBERON:0015488	88.81	gold quality
inferior vagus X ganglion	UBERON:0005363	88.57	silver quality
dorsal plus ventral thalamus	UBERON:0001897	88.41	silver quality
cardiac muscle of right atrium	UBERON:0003379	88.41	silver quality
medulla oblongata	UBERON:0001896	88.27	silver quality
trachea	UBERON:0003126	88.07	silver quality
cerebellar hemisphere	UBERON:0002245	87.97	gold quality
cerebellar cortex	UBERON:0002129	87.96	gold quality
left ventricle myocardium	UBERON:0006566	87.83	silver quality
subthalamic nucleus	UBERON:0001906	87.82	silver quality
cerebellum	UBERON:0002037	87.78	gold quality
superior vestibular nucleus	UBERON:0007227	87.72	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.50	gold quality
pituitary gland	UBERON:0000007	87.32	gold quality
tongue	UBERON:0001723	87.13	silver quality
superior surface of tongue	UBERON:0007371	87.11	gold quality
entorhinal cortex	UBERON:0002728	86.80	gold quality
dorsal root ganglion	UBERON:0000044	86.39	gold quality
pharyngeal mucosa	UBERON:0000355	86.30	silver quality
adenohypophysis	UBERON:0002196	86.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting PRR12, 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-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4728-5P	99.85	69.39	4718

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 3)

• This case represents the first constitutional balanced translocation disrupting and fusing both MIZ-type containing and proline-rich 12 and provides clues for the potential function and effects of these in the central nervous system. (PMID:26163108)
• Here we report on three unrelated patients with heterozygous de novo apparent loss-of-function mutations in PRR12 detected by clinical whole exome sequencing: c.1918G>T (p.Glu640*), c.4502_4505delTGCC (p.Leu1501Argfs*146) and c.903_909dup (p.Pro304Thrfs*46). All three patients had global developmental delay, intellectual disability, eye and vision abnormalities, dysmorphic features, and neuropsychiatric problems (PMID:29556724)
• Dominant variants in PRR12 result in unilateral or bilateral complex microphthalmia. (PMID:33314030)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prr12a	ENSDARG00000074229
danio_rerio	prr12b	ENSDARG00000075849
mus_musculus	Prr12	ENSMUSG00000046574
rattus_norvegicus	Prr12	ENSRNOG00000059408

Paralogs (1): QSER1 (ENSG00000060749)

Protein

Protein identifiers

Proline-rich protein 12 — Q9ULL5 (reviewed: Q9ULL5)

All UniProt accessions (1): Q9ULL5

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the regulation of cohesin complex loading onto chromatin, probably acting in coordination with NIPBL and MAU2.

Subunit / interactions. Interacts (via C-terminus) with NIPBL, MAU2 and the cohesin complex; the interaction with NIPBL is relevant for nuclear localization of the cohesin complex.

Subcellular location. Nucleus. Postsynaptic density. Synapse. Synaptosome.

Disease relevance. Neuroocular syndrome 1 (NOC1) [MIM:619539] An autosomal dominant form of neuroocular syndrome, a group of disorders characterized by developmental delay, impaired intellectual development and ocular anomalies as primary findings. Variable eye abnormalities include anophthalmia, microphthalmia, and coloboma. Other common features include congenital heart and kidney defects, hypotonia, failure to thrive, and microcephaly. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULL5-3	1	yes
Q9ULL5-2	2

RefSeq proteins (1): NP_065770* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025451	DUF4211	Domain
IPR052466	DNA_MethProtect_Complex	Family

Pfam: PF13926

UniProt features (66 total): compositionally biased region 28, modified residue 17, region of interest 11, sequence variant 8, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULL5-F1	43.84	0.11

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 (17): 332, 340, 651, 738, 865, 1077, 1135, 1223, 1304, 1308, 1381, 1382, 1387, 1561, 1568, 1705, 1925

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 265 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD11B_DC_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOCC_NEURON_PROJECTION, GOCC_POSTSYNAPSE, GOCC_SYNAPSE, GOCC_NEURON_TO_NEURON_SYNAPSE, ATF6_TARGET_GENES, ELF2_TARGET_GENES, FOXD2_TARGET_GENES, GLI3_TARGET_GENES, H1_6_TARGET_GENES, ID2_TARGET_GENES, NAB2_TARGET_GENES, PCGF1_TARGET_GENES

GO Biological Process (1): intracellular protein localization (GO:0008104)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), postsynaptic density (GO:0014069), neuron projection (GO:0043005), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macromolecule localization	1
binding	1
intracellular membrane-bounded organelle	1
asymmetric synapse	1
postsynaptic specialization	1
plasma membrane bounded cell projection	1
cell junction	1

Protein interactions and networks

STRING

818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRR12	PRRG2	O14669	598
PRR12	PRR16	Q569H4	540
PRR12	CTAGE8	P0CG41	511
PRR12	PAGR1	Q9BTK6	484
PRR12	SCAF1	Q9H7N4	427
PRR12	CSN1S1	P47710	418
PRR12	INSC	Q1MX18	412
PRR12	INAFM1	C9JVW0	404
PRR12	GPRASP2	Q96D09	396
PRR12	TSKS	Q9UJT2	394
PRR12	ZFHX4	Q86UP3	383
PRR12	RNF14	Q9UBS8	381
PRR12	NAA38	Q9BRA0	379
PRR12	ZNF317	Q96PQ6	377
PRR12	SEC24A	O95486	374

IntAct

60 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
PRR12	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
	DENR	psi-mi:“MI:0915”(physical association)	0.400
PRR12	FASN	psi-mi:“MI:0915”(physical association)	0.370
PUM1	PRR12	psi-mi:“MI:0915”(physical association)	0.370
NCBP3	RSL1D1	psi-mi:“MI:0914”(association)	0.350
NCBP2	SEH1L	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MED19	psi-mi:“MI:0914”(association)	0.350
ARHGAP12	WASL	psi-mi:“MI:0914”(association)	0.350
FGL1	DNM1L	psi-mi:“MI:0914”(association)	0.350
MAGEA10	KANSL1L	psi-mi:“MI:0914”(association)	0.350
SLC15A3	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
AR	MED6	psi-mi:“MI:2364”(proximity)	0.270
RAVER1	KDM6A	psi-mi:“MI:2364”(proximity)	0.270
CTBP1	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270
	JUN	psi-mi:“MI:2364”(proximity)	0.270
TBXT	BCL9	psi-mi:“MI:2364”(proximity)	0.270
ERG	BCL9	psi-mi:“MI:2364”(proximity)	0.270
ETV4	BCL9	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
FOXI1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
FOXL1	PGRMC1	psi-mi:“MI:2364”(proximity)	0.270
GATA2	BCL9	psi-mi:“MI:2364”(proximity)	0.270
GATA3	BCL9	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (140): PRR12 (Proximity Label-MS), PRR12 (Affinity Capture-MS), PRR12 (Affinity Capture-MS), PRR12 (Affinity Capture-MS), PRR12 (Affinity Capture-MS), PRR12 (Affinity Capture-MS), PRR12 (Proximity Label-MS), PRR12 (Proximity Label-MS), PRR12 (Affinity Capture-RNA), PRR12 (Affinity Capture-MS), PRR12 (Affinity Capture-MS), PRR12 (Affinity Capture-MS), PRR12 (Proximity Label-MS), PRR12 (Proximity Label-MS), PRR12 (Proximity Label-MS)

ESM2 similar proteins: A1YFU7, A2AJK6, A2BH40, A3RK75, D3YWE6, E9PYL2, E9Q4N7, O00512, O14497, O15417, O35126, O35740, O43365, P02831, P09026, P09027, P14651, P25822, P31249, P48634, P54258, P54259, P78414, P81068, P91613, P91716, P92203, Q06A37, Q08DG7, Q0VCT9, Q10571, Q24248, Q3UHR0, Q5IS70, Q5TM26, Q67FY3, Q7TQ40, Q80WC3, Q8CFT2, Q8NFD5

Diamond homologs: A0A338P6K9, E9PYL2, Q2KHR3, Q66IN2, Q9ULL5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
Deactivation of the beta-catenin transactivating complex	6	25.0×	6e-05
TCF dependent signaling in response to WNT	5	10.5×	6e-03
Signaling by WNT	5	10.0×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
neuron fate specification	5	46.2×	1e-05
positive regulation of miRNA transcription	6	22.9×	3e-05
inner ear morphogenesis	5	19.8×	2e-04
somatic stem cell population maintenance	5	16.3×	6e-04
anatomical structure morphogenesis	7	12.8×	8e-05
transcription by RNA polymerase II	13	12.1×	1e-08
male gonad development	5	10.3×	3e-03
chromatin remodeling	9	8.6×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	25
Uncertain significance	420
Likely benign	191
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013591	NM_020719.3(PRR12):c.4674_4676delinsGC (p.Cys1558fs)	Pathogenic
1013592	NM_020719.3(PRR12):c.3273del (p.Lys1092fs)	Pathogenic
1013593	NM_020719.3(PRR12):c.3224del (p.Thr1075fs)	Pathogenic
1013594	NM_020719.3(PRR12):c.2755C>T (p.Gln919Ter)	Pathogenic
1013595	NM_020719.3(PRR12):c.2398dup (p.Gln800fs)	Pathogenic
1013596	NM_020719.3(PRR12):c.2236_2237del (p.Val746fs)	Pathogenic
1013597	NM_020719.3(PRR12):c.790C>T (p.Gln264Ter)	Pathogenic
1013598	NM_020719.3(PRR12):c.334dup (p.Gln112fs)	Pathogenic
1184840	NM_020719.3(PRR12):c.677dup (p.Tyr227fs)	Pathogenic
1309310	NM_020719.3(PRR12):c.5441dup (p.Pro1816fs)	Pathogenic
1311039	NM_020719.3(PRR12):c.3647dup (p.Thr1217fs)	Pathogenic
1676830	NM_020719.3(PRR12):c.1521T>G (p.Tyr507Ter)	Pathogenic
1676831	NM_020719.3(PRR12):c.3958C>T (p.Arg1320Ter)	Pathogenic
1694935	NM_020719.3(PRR12):c.1255_1256del (p.Ser419fs)	Pathogenic
1699083	NM_020719.3(PRR12):c.4344del (p.Glu1449fs)	Pathogenic
1701759	NM_020719.3(PRR12):c.2680_2695dup (p.Val899fs)	Pathogenic
1708253	NM_020719.3(PRR12):c.931C>T (p.Gln311Ter)	Pathogenic
2227865	NM_020719.3(PRR12):c.2946dup (p.Gly983fs)	Pathogenic
2388377	NM_020719.3(PRR12):c.2345_2348del (p.Leu782fs)	Pathogenic
2412950	NM_020719.3(PRR12):c.2732_2744del (p.Gly911fs)	Pathogenic
2498790	NM_020719.3(PRR12):c.1570del (p.Leu524fs)	Pathogenic
2571051	NM_020719.3(PRR12):c.2281C>T (p.Gln761Ter)	Pathogenic
2578838	NM_020719.3(PRR12):c.1441_1450del (p.Gln481fs)	Pathogenic
2687488	NM_020719.3(PRR12):c.1549_1568del (p.Pro517fs)	Pathogenic
2833997	NM_020719.3(PRR12):c.5041A>T (p.Lys1681Ter)	Pathogenic
3027175	NM_020719.3(PRR12):c.1507C>T (p.Gln503Ter)	Pathogenic
3058161	NM_020719.3(PRR12):c.1441C>T (p.Gln481Ter)	Pathogenic
3061967	NM_020719.3(PRR12):c.521del (p.Pro174fs)	Pathogenic
3065991	NM_020719.3(PRR12):c.1205del (p.Gly402fs)	Pathogenic
3343930	NM_020719.3(PRR12):c.1479_1480del (p.Cys494fs)	Pathogenic

SpliceAI

2092 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49591736:GCTAG:G	donor_gain	1.0000
19:49591737:C:G	donor_gain	1.0000
19:49591741:G:GC	donor_loss	1.0000
19:49591742:T:G	donor_loss	1.0000
19:49593324:CA:C	acceptor_loss	1.0000
19:49593325:A:AG	acceptor_gain	1.0000
19:49593325:AGCTT:A	acceptor_gain	1.0000
19:49593326:G:GA	acceptor_gain	1.0000
19:49593326:G:GT	acceptor_loss	1.0000
19:49593326:GC:G	acceptor_gain	1.0000
19:49593326:GCT:G	acceptor_gain	1.0000
19:49593326:GCTT:G	acceptor_gain	1.0000
19:49593326:GCTTG:G	acceptor_gain	1.0000
19:49593437:CAGG:C	donor_loss	1.0000
19:49593438:AGGT:A	donor_loss	1.0000
19:49593439:GGTA:G	donor_loss	1.0000
19:49593440:GT:G	donor_loss	1.0000
19:49593441:T:G	donor_loss	1.0000
19:49594449:GCCA:G	acceptor_loss	1.0000
19:49594450:CCAG:C	acceptor_loss	1.0000
19:49594451:CAG:C	acceptor_loss	1.0000
19:49594452:A:AG	acceptor_gain	1.0000
19:49594452:AGG:A	acceptor_loss	1.0000
19:49594453:G:GG	acceptor_gain	1.0000
19:49601915:CAAGG:C	donor_loss	1.0000
19:49601917:AGGT:A	donor_loss	1.0000
19:49601920:T:A	donor_loss	1.0000
19:49614530:CAGCT:C	acceptor_loss	1.0000
19:49614531:A:AG	acceptor_gain	1.0000
19:49614531:AGCT:A	acceptor_gain	1.0000

AlphaMissense

12894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49594526:T:C	L91P	1.000
19:49596256:T:C	F641L	1.000
19:49596257:T:C	F641S	1.000
19:49596258:C:A	F641L	1.000
19:49596258:C:G	F641L	1.000
19:49596272:T:C	L646P	1.000
19:49597130:T:A	I932N	1.000
19:49597132:T:C	C933R	1.000
19:49597133:G:A	C933Y	1.000
19:49597134:C:G	C933W	1.000
19:49597135:T:C	F934L	1.000
19:49597136:T:C	F934S	1.000
19:49597136:T:G	F934C	1.000
19:49597137:C:A	F934L	1.000
19:49597137:C:G	F934L	1.000
19:49597525:T:C	F1064L	1.000
19:49597526:T:C	F1064S	1.000
19:49597527:C:A	F1064L	1.000
19:49597527:C:G	F1064L	1.000
19:49597528:T:C	C1065R	1.000
19:49597529:G:A	C1065Y	1.000
19:49597530:C:G	C1065W	1.000
19:49597553:T:A	L1073H	1.000
19:49597553:T:C	L1073P	1.000
19:49597557:G:C	K1074N	1.000
19:49597557:G:T	K1074N	1.000
19:49597567:T:C	F1078L	1.000
19:49597569:C:A	F1078L	1.000
19:49597569:C:G	F1078L	1.000
19:49597574:T:C	L1080P	1.000

dbSNP variants (sampled 300 via entrez): RS1000012404 (19:49592411 C>T), RS1000082702 (19:49590226 G>A), RS1000085512 (19:49592643 T>C), RS1000167770 (19:49606639 A>C,G,T), RS1000173630 (19:49610397 C>G), RS1000317524 (19:49611297 C>G,T), RS1000433751 (19:49611573 G>A), RS1000686722 (19:49605186 G>C), RS1000725287 (19:49600884 C>T), RS1000756496 (19:49616454 C>T), RS1000784241 (19:49617522 T>C), RS1000786509 (19:49597780 C>A,G,T), RS1000861328 (19:49589281 C>T), RS1001067930 (19:49593736 A>G), RS1001090826 (19:49590870 G>C)

Disease associations

OMIM: gene MIM:616633 | disease phenotypes: MIM:619539, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
neuroocular syndrome	Definitive	Autosomal dominant
neuroocular syndrome 1	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
neuroocular syndrome	Definitive	AD

Mondo (5): neuroocular syndrome (MONDO:0859193), neuroocular syndrome 1 (MONDO:0971007), intellectual disability (MONDO:0001071), autism (MONDO:0005260), coloboma of iris (MONDO:0020356)

Orphanet (3): Multiple congenital anomalies-neurodevelopmental delay-ocular abnormalities syndrome (Orphanet:659904), Coloboma of iris (Orphanet:98944), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000176	Submucous cleft hard palate
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000336	Prominent supraorbital ridges
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000482	Microcornea
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000527	Long eyelashes
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000568	Microphthalmia
HP:0000574	Thick eyebrow
HP:0000577	Exotropia
HP:0000579	Nasolacrimal duct obstruction
HP:0000612	Iris coloboma
HP:0000635	Blue irides
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000659	Peters anomaly
HP:0000664	Synophrys
HP:0000687	Widely spaced teeth
HP:0000729	Autistic behavior
HP:0000739	Anxiety

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002539_91	Schizophrenia	5.000000e-08
GCST003194_32	Fibrinogen levels	2.000000e-08
GCST006803_99	Schizophrenia	4.000000e-11
GCST007278_25	Systemic seropositive rheumatic diseases (Systemic sclerosis or systemic lupus erythematosus or rheumatoid arthritis or idiopathic inflammatory myopathies)	3.000000e-08
GCST010242_219	HDL cholesterol levels	8.000000e-09
GCST012335_15	Hodgkin’s lymphoma	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725158 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.92	IC50	120	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178828: Inhibition of PRR12 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
sodium arsenite	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
Acrolein	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	affects methylation	1
Ozone	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vincristine	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697558	Binding	Inhibition of PRR12 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder