PRDM12

Summary

PRDM12 (PR/SET domain 12, HGNC:13997) is a protein-coding gene on chromosome 9q34.12, encoding PR domain zinc finger protein 12 (Q9H4Q4). Transcriptional regulator necessary for the development of nociceptive neurons, playing a key role in determining the nociceptive lineage from neural crest cell progenitors.

This gene encodes a transcriptional regulator of sensory neuronal specification that plays a critical role in pain perception. The encoded protein contains an N-terminal PRDI-BF1 and RIZ homology (PR) domain, a SET domain, and three C-terminal C2H2 zinc finger DNA-binding domains. Naturally occurring mutations in this gene are associated with congenital insensitivity to pain (CIP), and hereditary sensory and autonomic neuropathies (HSAN’s) affecting peripheral sensory and autonomic neurons. Deregulation of this gene is associated with solid cancers and hematological malignancies including chronic myeloid leukaemia.

Source: NCBI Gene 59335 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary sensory and autonomic neuropathy (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 297 total — 12 pathogenic, 5 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 18
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.15 (unconstrained)
• MANE Select transcript: NM_021619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13997
Approved symbol	PRDM12
Name	PR/SET domain 12
Location	9q34.12
Locus type	gene with protein product
Status	Approved
Aliases	PFM9
Ensembl gene	ENSG00000130711
Ensembl biotype	protein_coding
OMIM	616458
Entrez	59335

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000253008

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000253008, ENST00000676323

RefSeq mRNA: 1 — MANE Select: NM_021619 NM_021619

CCDS: CCDS6934

Canonical transcript exons

ENST00000253008 — 5 exons

Exon	Start	End
ENSE00000868121	130664594	130664876
ENSE00000868122	130666608	130666798
ENSE00000868123	130668158	130668313
ENSE00000868124	130678529	130678640
ENSE00001052791	130681248	130682983

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 88.71.

Highest expression (Bgee): type B pancreatic cell, buccal mucosa cell, olfactory bulb, skeletal muscle tissue of rectus abdominis, cervix squamous epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRDM12 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adrenal Gland	eqtl	1.6e-02	+0.28	9:131371615:T:C
Brain Cerebellar Hemisphere	eqtl	2.0e-02	-0.72	9:130902374:C:T

Top tissues by expression

showing 100 of 215 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	88.71	gold quality
buccal mucosa cell	CL:0002336	86.87	gold quality
olfactory bulb	UBERON:0002264	85.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.28	silver quality
cervix squamous epithelium	UBERON:0006922	78.72	gold quality
diaphragm	UBERON:0001103	77.20	gold quality
vena cava	UBERON:0004087	76.82	silver quality
vastus lateralis	UBERON:0001379	76.48	gold quality
thymus	UBERON:0002370	76.22	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.92	gold quality
trachea	UBERON:0003126	75.16	gold quality
substantia nigra pars compacta	UBERON:0001965	74.95	silver quality
triceps brachii	UBERON:0001509	74.71	gold quality
cerebellar vermis	UBERON:0004720	74.67	gold quality
cardia of stomach	UBERON:0001162	74.34	gold quality
pericardium	UBERON:0002407	74.34	silver quality
biceps brachii	UBERON:0001507	74.15	gold quality
lateral nuclear group of thalamus	UBERON:0002736	74.05	gold quality
pons	UBERON:0000988	73.98	gold quality
pylorus	UBERON:0001166	73.93	gold quality
superior surface of tongue	UBERON:0007371	73.83	gold quality
penis	UBERON:0000989	73.13	silver quality
male germ cell	CL:0000015	72.86	gold quality
renal medulla	UBERON:0000362	72.81	gold quality
globus pallidus	UBERON:0001875	72.36	silver quality
cervix epithelium	UBERON:0004801	72.04	gold quality
medial globus pallidus	UBERON:0002477	71.93	silver quality
gluteal muscle	UBERON:0002000	71.83	gold quality
tongue squamous epithelium	UBERON:0006919	71.80	gold quality
sperm	CL:0000019	71.73	gold quality
hair follicle	UBERON:0002073	71.42	gold quality
tendon of biceps brachii	UBERON:0008188	69.24	gold quality
upper arm skin	UBERON:0004263	68.69	gold quality
epithelium of nasopharynx	UBERON:0001951	67.96	gold quality
oocyte	CL:0000023	67.95	gold quality
jejunum	UBERON:0002115	67.57	silver quality
epithelium of mammary gland	UBERON:0003244	66.72	gold quality
mammary duct	UBERON:0001765	66.64	gold quality
superficial temporal artery	UBERON:0001614	66.32	gold quality
parotid gland	UBERON:0001831	65.97	gold quality
epithelial cell of pancreas	CL:0000083	65.95	gold quality
mucosa of urinary bladder	UBERON:0001259	64.47	gold quality
nephron tubule	UBERON:0001231	63.89	gold quality
layer of synovial tissue	UBERON:0007616	63.39	gold quality
renal glomerulus	UBERON:0000074	63.19	gold quality
metanephric glomerulus	UBERON:0004736	63.13	gold quality
oral cavity	UBERON:0000167	63.10	gold quality
kidney epithelium	UBERON:0004819	63.01	gold quality
orbitofrontal cortex	UBERON:0004167	62.87	gold quality
squamous epithelium	UBERON:0006914	62.22	gold quality
mammalian vulva	UBERON:0000997	61.86	gold quality
secondary oocyte	CL:0000655	61.82	gold quality
blood vessel layer	UBERON:0004797	61.69	silver quality
trabecular bone tissue	UBERON:0002483	61.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	61.27	gold quality
gingiva	UBERON:0001828	61.10	gold quality
heart right ventricle	UBERON:0002080	60.89	gold quality
tibia	UBERON:0000979	60.83	gold quality
nasal cavity epithelium	UBERON:0005384	60.63	gold quality
CA1 field of hippocampus	UBERON:0003881	60.40	gold quality
periodontal ligament	UBERON:0008266	60.18	gold quality
endothelial cell	CL:0000115	59.86	gold quality
left ventricle myocardium	UBERON:0006566	59.82	gold quality
adult organism	UBERON:0007023	59.58	silver quality
gingival epithelium	UBERON:0001949	59.49	gold quality
palpebral conjunctiva	UBERON:0001812	59.39	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	59.25	gold quality
jejunal mucosa	UBERON:0000399	59.07	gold quality
colonic mucosa	UBERON:0000317	58.72	gold quality
seminal vesicle	UBERON:0000998	58.64	silver quality
visceral pleura	UBERON:0002401	58.55	gold quality
epithelium of esophagus	UBERON:0001976	58.54	gold quality
inferior olivary complex	UBERON:0002127	58.37	gold quality
parietal pleura	UBERON:0002400	58.30	gold quality
pleura	UBERON:0000977	58.08	gold quality
mucosa of sigmoid colon	UBERON:0004993	58.04	gold quality
skin of hip	UBERON:0001554	57.87	silver quality
mammary gland	UBERON:0001911	57.06	gold quality
thoracic mammary gland	UBERON:0005200	56.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	56.78	gold quality
prefrontal cortex	UBERON:0000451	56.54	gold quality
esophagus squamous epithelium	UBERON:0006920	56.54	gold quality
hypothalamus	UBERON:0001898	56.50	gold quality
cartilage tissue	UBERON:0002418	56.11	gold quality
frontal cortex	UBERON:0001870	55.43	gold quality
pigmented layer of retina	UBERON:0001782	55.38	gold quality
middle temporal gyrus	UBERON:0002771	55.19	gold quality
duodenum	UBERON:0002114	54.23	gold quality
cerebral cortex	UBERON:0000956	53.93	gold quality
neocortex	UBERON:0001950	53.79	gold quality
temporal lobe	UBERON:0001871	53.64	silver quality
metanephros	UBERON:0000081	53.26	gold quality
midbrain	UBERON:0001891	52.99	silver quality
primary visual cortex	UBERON:0002436	52.28	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	52.14	gold quality
telencephalon	UBERON:0001893	52.09	gold quality
Ammon’s horn	UBERON:0001954	51.73	gold quality
bone marrow	UBERON:0002371	51.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.44	gold quality
cortical plate	UBERON:0005343	51.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.48

HPA expression

RNA tissue specificity: Tissue enriched

14 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Septum	tissue	4.7
Hypothalamus	tissue	1.6
Postcentral gyrus	tissue	0.8
Locus coeruleus	tissue	0.6
Nucleus accumbens	tissue	0.4
Hippocampus	tissue	0.4
Ventral forebrain	tissue	0.4
Pituitary gland	tissue	0.1
Pancreas	tissue	0.1
Frontal cortex	tissue	0.1
Choroid plexus	tissue	0.1
Midbrain	tissue	0.1
Spinal cord	tissue	0.1
Caudate putamen	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 181; highest nTPM — Septal nuclei (5.5), Arcuate nucleus (4.4), Nucleus of the diagonal band (3.1), Paraventricular nucleus (2.8), Dorsomedial nucleus (1.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PRDM12 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 50 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-6803-5P	99.19	63.90	1026

Functional genomics

gnomAD constraint: pLI 2.37e-05, LOEUF 1.15, missense Z 0.247 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000253008 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
9:130,664,654–130,681,332	300 / 350.0	0.86	no
9:130,681,333–130,681,364	4 / 17.0	0.24	yes (p 1.6e-03)
9:130,681,365–130,681,400	28 / 18.3	1.53	no
9:130,681,401–130,681,529	24 / 64.0	0.38	no
9:130,681,530–130,681,666	66 / 61.5	1.07	no

Literature-anchored findings (GeneRIF, showing 7)

• Down-regulation of PRDM12 is associated with the pathogenesis of chronic myeloid leukaemia with derivative chromosome 9 deletion (PMID:14523459)
• PRDM12 and its functional fly homolog Hamlet are evolutionary conserved master regulators of sensory neuronal specification and play a critical role in pain perception (PMID:25891934)
• Prdm12 is a key factor in the orchestration of sensory neurogenesis. (PMID:26005867)
• The natural history of the PRDM12-CIP disorder. (PMID:26975306)
• Study in five further children, from four families, with facial lesions typical of midface toddler excoriation syndrome (MiTES) found autosomal recessive mutations in PRDM12 in four of five patients and extended the phenotypic spectrum of PRDM12 mutations, which usually cause hereditary sensory and autonomic neuropathy type VIII, characterized by mutilating self-inflicted wounds of the extremities, lips and tongue. (PMID:29949203)
• PRDM12 in Health and Diseases. (PMID:34769459)
• Ocular manifestations among patients with congenital insensitivity to pain due to variants in PRDM12 and SCN9A genes. (PMID:36111846)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdm12b	ENSDARG00000007430
mus_musculus	Prdm12	ENSMUSG00000079466
rattus_norvegicus	Prdm12	ENSRNOG00000009218

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685844) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
small dorsal root ganglion	1
decreased sensory neuron number	1
small trigeminal ganglion	1
abnormal superior glossopharyngeal ganglion morphology	1
decreased locomotor activity	1
decreased exploration in new environment	1
abnormal embryo size	1
increased neuron apoptosis	1
increased circulating cholesterol level	1
abnormal neurite morphology	1
decreased neuron number	1
shortened QRS complex duration	1
neonatal lethality, complete penetrance	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	A6QPM3	93.1%	Diamond
Caenorhabditis elegans	A0A163UT06	42.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FUBP3	protein-coding	8939
FIBCD1-AS1	ncRNA	105376297
EXOSC2	protein-coding	23404
ABL1	protein-coding	25
QRFP	protein-coding	347148
FIBCD1	protein-coding	84929
MIR6856	ncRNA	102465515
ASS1	protein-coding	445

Protein

Protein identifiers

PR domain zinc finger protein 12 — Q9H4Q4 (reviewed: Q9H4Q4)

Alternative names: PR domain-containing protein 12

All UniProt accessions (2): A0A6Q8PH01, Q9H4Q4

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator necessary for the development of nociceptive neurons, playing a key role in determining the nociceptive lineage from neural crest cell progenitors. Initiates neurogenesis and activates downstream pro-neuronal transcription factors, such as NEUROD1, BRN3A, and ISL1, specifically within nociceptive neurons, while repressing non-nociceptor cell fates. Essential for the proper function of nociceptors in adults, influencing both their excitability and their gene expression, thereby impacting how these neurons respond to various pain stimuli.

Subunit / interactions. Interacts with EHMT2.

Subcellular location. Nucleus.

Tissue specificity. Not found in adult tissues except in dorsal root ganglia.

Disease relevance. Neuropathy, hereditary sensory and autonomic, 8 (HSAN8) [MIM:616488] A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN8 patients manifest congenital insensitivity to pain resulting in ulceration to the fingers, tongue, lips, and other distal appendages. Some patients may also have decreased sweating and tear production. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. The poly-alanine tract is polymorphic in the general population and contains a maximum of 14 alanines.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily.

RefSeq proteins (1): NP_067632* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Zf-C2H2_type	Domain
IPR017126	Znf_PRDM12	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044406	PRDM12_PR/SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF21549

UniProt features (26 total): strand 11, sequence variant 7, zinc finger region 3, chain 1, domain 1, helix 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
3EP0	Methyltransferase domain of human PR domain-containing protein 12	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4Q4-F1	64.81	0.12

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH uncertain · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 147 (showing top): CREL_01, BENPORATH_ES_WITH_H3K27ME3, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_NEUROGENESIS, EFC_Q6, NFKB_Q6, GOBP_SENSORY_PERCEPTION_OF_PAIN, CDP_01, GOBP_DETECTION_OF_TEMPERATURE_STIMULUS, ATF1_Q6, GOBP_NEURON_FATE_SPECIFICATION, TGANTCA_AP1_C, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, NKX22_01, TATA_C

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA-templated transcription (GO:0006351), protein methylation (GO:0006479), regulation of gene expression (GO:0010468), sensory perception of pain (GO:0019233), neurogenesis (GO:0022008), neuron projection development (GO:0031175), neuron fate specification (GO:0048665), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (10): DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), zinc ion binding (GO:0008270), histone chaperone activity (GO:0140713), histone methyltransferase binding (GO:1990226), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), protein binding (GO:0005515), methyltransferase activity (GO:0008168), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

35 GO namespaces:

Category	Terms
regulation of transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
gene expression	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
RNA biosynthetic process	1
protein alkylation	1
macromolecule methylation	1
regulation of macromolecule biosynthetic process	1
sensory perception	1
nervous system development	1
cell differentiation	1
neuron development	1
plasma membrane bounded cell projection organization	1
cell fate specification	1
neuron fate commitment	1
sensory perception of pain	1
detection of temperature stimulus involved in sensory perception	1
positive regulation of DNA-templated transcription	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
histone binding	1
protein carrier activity	1
enzyme binding	1
chromatin	1
DNA-binding transcription factor activity	1
binding	1
transferase activity, transferring one-carbon groups	1
cation binding	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
detection of temperature stimulus involved in sensory perception of pain	BP	mutant phenotype
neuron projection development	BP	mutant phenotype
protein methylation	BP	direct assay
sensory perception of pain	BP	mutant phenotype
nucleus	CC	direct assay
histone chaperone activity	MF	direct assay
histone methyltransferase binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 514 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM12	PHOX2B	Q99453	615
PRDM12	DRGX	A6NNA5	567
PRDM12	PRDM11	Q9NQV5	547
PRDM12	AVIL	O75366	539
PRDM12	P2RX3	P56373	523
PRDM12	DBX1	A6NMT0	503
PRDM12	SCN11A	Q9UI33	500
PRDM12	SCN9A	Q15858	498
PRDM12	ASIC3	Q9UHC3	473
PRDM12	STK32A	Q8WU08	472
PRDM12	POU4F1	Q01851	449
PRDM12	CREG2	Q8IUH2	438
PRDM12	SOX10	P56693	431
PRDM12	NTRK1	P04629	428
PRDM12	OR11L1	Q8NGX0	407

IntAct

Human interaction partners of PRDM12 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
SERPINB8	association	0.350	1

BioGRID (5 interactions; top human partners by supporting records): EZH2 (Affinity Capture-MS), PARP1 (Proximity Label-MS), PARP2 (Proximity Label-MS), RUNX1T1 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for PRDM12: 297 ClinVar records (17 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	5
Uncertain significance	141
Likely benign	102
Benign	20

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 17 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
253121	NM_021619.3(PRDM12):c.516G>C (p.Glu172Asp)	Pathogenic	criteria provided, single submitter	2
1072417	NM_021619.3(PRDM12):c.224-1G>A	Pathogenic	criteria provided, single submitter	1
1323492	NM_021619.3(PRDM12):c.131_138del (p.Val44fs)	Pathogenic	criteria provided, single submitter	1
1332705	NM_021619.3(PRDM12):c.785T>G (p.Met262Arg)	Pathogenic	criteria provided, single submitter	1
1745663	NM_021619.3(PRDM12):c.514G>T (p.Glu172Ter)	Pathogenic	criteria provided, single submitter	1
2706647	NM_021619.3(PRDM12):c.578dup (p.Pro194fs)	Pathogenic	criteria provided, single submitter	1
4855324	NM_021619.3(PRDM12):c.563_564insTGATCGGCACCAGCATCTTCTACAAGGC (p.Ile189fs)	Pathogenic	criteria provided, single submitter	1
430206	NM_021619.3(PRDM12):c.811T>G (p.Phe271Val)	Likely pathogenic	criteria provided, single submitter	1
451909	NM_021619.3(PRDM12):c.600_606delinsCA (p.Trp201fs)	Likely pathogenic	criteria provided, single submitter	1
848182	NM_021619.3(PRDM12):c.1041CGC[18] (p.Ala354_Ala359dup)	Likely pathogenic	criteria provided, single submitter	1
3773873	NM_021619.3(PRDM12):c.455C>A (p.Ala152Asp)	Likely pathogenic	criteria provided, single submitter	1
4904914	NM_021619.3(PRDM12):c.178A>T (p.Lys60Ter)	Likely pathogenic	criteria provided, single submitter	1
59908	GRCh38/hg38 9q34.11-34.3(chr9:129068560-136495351)x3	Pathogenic	criteria provided, single submitter	1
253118	NM_021619.3(PRDM12):c.1041CGC[(15_?)]	Pathogenic	no assertion criteria provided	1
253120	NM_021619.3(PRDM12):c.91G>T (p.Asp31Tyr)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PRDM12’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 376):

Position(s)	Effect	Δscore	Sites
9:130666796	donor_gain	1.0000
9:130666799–130666800	donor_loss	1.0000	4
9:130668156–130668157	acceptor_loss	1.0000	5
9:130668314–130668315	donor_loss	1.0000	5
9:130678527–130678528	acceptor_loss	1.0000	5
9:130678641–130678642	donor_loss	1.0000	5
9:130681210	acceptor_gain	1.0000
9:130681224	acceptor_gain	1.0000
9:130681242	acceptor_gain	1.0000
9:130664877–130664878	donor_loss	0.9900	5

AlphaMissense

1,199 missense substitutions predicted likely pathogenic (of 2,410 scored), across 281 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M161	9	0.889	0.987
M262	9	0.858	0.980
H261	8	0.997	0.999
H289	8	0.996	0.999
H265	8	0.995	0.998
H293	8	0.984	0.997
F252	8	0.970	1.000
F280	8	0.963	1.000
F103	8	0.962	0.998
H317	8	0.950	0.990
D151	8	0.889	0.965
N257	8	0.880	0.993
N169	8	0.875	0.980
N288	8	0.875	0.991
S281	8	0.861	0.992
D268	8	0.860	0.975
N174	8	0.821	0.957
D31	8	0.775	0.938
C248	7	0.999	1.000
C245	7	0.997	1.000

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:616458 | disease phenotypes: MIM:616488

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hereditary sensory and autonomic neuropathy	Definitive	Autosomal recessive
congenital insensitivity to pain-hypohidrosis syndrome	Definitive	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
DDG2P	green
Familial dysautonomia	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Paediatric disorders	green
Pain syndromes	green

Mondo (2): congenital insensitivity to pain-hypohidrosis syndrome (MONDO:0014662), hereditary sensory and autonomic neuropathy (MONDO:0015364)

Orphanet (1): Hereditary sensory and autonomic neuropathy type 8 (Orphanet:478664)

HPO phenotypes

18 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000559	Corneal scarring
HP:0000633	Decreased lacrimation
HP:0000966	Hypohidrosis
HP:0001249	Intellectual disability
HP:0001265	Hyporeflexia
HP:0001581	Recurrent skin infections
HP:0002495	Impaired vibratory sensation
HP:0002579	Gastrointestinal dysmotility
HP:0003593	Infantile onset
HP:0004409	Hyposmia
HP:0007021	Pain insensitivity
HP:0010829	Impaired temperature sensation
HP:0010831	Impaired proprioception
HP:0011463	Childhood onset
HP:0012804	Corneal ulceration
HP:0033748	Hypoesthesia

GWAS associations

2 associations:

Study	Trait	p-value
GCST008839_84	Height	8e-28
GCST002304_7	Fractional exhaled nitric oxide (childhood)	5e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005536	nitric oxide exhalation measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D009477	Hereditary Sensory and Autonomic Neuropathies	C10.500.250; C10.574.500.493; C10.668.829.800.175; C16.131.666.310; C16.320.400.415

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5214854 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation, increases mutagenesis	3
Aflatoxin B1	increases expression, increases methylation	2
hydroxyhydroquinone	decreases expression, decreases reaction	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ferrous chloride	decreases expression	1
4-aminobenzhydrazide	decreases expression, decreases reaction	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	increases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cadmium Chloride	increases expression	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5214661	Binding	Selectivity interaction (Methyltransferase panel (DSF assay)) EUB0000234b PRDM12	Selectivity Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HC90	HEK293 eGFP-PRDM12	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

3 trials:

NCT	Phase	Status	Title
NCT02624310	Phase 2	WITHDRAWN	A Study of Norepinephrine in Patients With Congenital Insensitivity to Pain and Anhidrosis
NCT02696746	Not specified	UNKNOWN	Painful Channelopathies Study
NCT03920774	Not specified	RECRUITING	The Natural History of Familial Dysautonomia