NPFF

Summary

NPFF (neuropeptide FF-amide peptide precursor, HGNC:7901) is a protein-coding gene on chromosome 12q13.13, encoding Pro-FMRFamide-related neuropeptide FF (O15130). Morphine modulating peptides.

This gene encodes a member of the FMRFamide related peptide (FARP) family of neuropeptides. The encoded preproprotein is proteolytically processed to generate multiple amidated peptides. These peptides may play a role in the regulation of heart rate and blood pressure and the modulation of morphine-induced antinociception. Patients with hypertension exhibit decreased expression of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 8620 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 1 total
• GTEx eGene: eQTL in 7 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.73 (unconstrained)
• MANE Select transcript: NM_003717

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7901
Approved symbol	NPFF
Name	neuropeptide FF-amide peptide precursor
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	FMRFAL
Ensembl gene	ENSG00000139574
Ensembl biotype	protein_coding
OMIM	604643
Entrez	8620

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

MANE Select: ENST00000267017

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000267017, ENST00000448979, ENST00000940394, ENST00001142754

RefSeq mRNA: 2 — MANE Select: NM_003717 NM_001320296, NM_003717

CCDS: CCDS8862

Canonical transcript exons

ENST00000267017 — 3 exons

Exon	Start	End
ENSE00000938816	53507373	53507484
ENSE00002382266	53506688	53506893
ENSE00003459631	53507021	53507142

Expression profiles

Bgee: expression breadth ubiquitous, 104 present calls, max score 90.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1823 / max 224.5907, expressed in 35 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, colonic epithelium, granulocyte, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NPFF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

9 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Spinal cord cervical c-1	eqtl	1.4e-03	+1.17	12:53836195:C:A
Esophagus Gastroesophageal Junction	eqtl	1.6e-03	-0.22	12:53287171:C:T
Prostate	eqtl	1.3e-02	-0.16	12:53566405:A:G
Testis	eqtl	1.4e-02	-0.13	12:53676278:C:CTG
Brain Cerebellum	eqtl	1.5e-02	-0.19	12:53957592:CG:C
Ovary	eqtl	2.5e-02	-0.27	12:53642530:C:T
Brain Hypothalamus	eqtl	2.7e-02	+0.51	12:54443686:G:A
Brain Substantia nigra	sqtl	4.5e-02	-3.25	12:52555628:A:G
Adipose Subcutaneous	sqtl	4.5e-02	-0.82	12:53150475:T:TA

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
131248	0.1823	35

Top tissues by expression

showing 100 of 123 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.94	gold quality
colonic epithelium	UBERON:0000397	60.93	gold quality
granulocyte	CL:0000094	55.36	gold quality
ganglionic eminence	UBERON:0004023	54.55	gold quality
cortical plate	UBERON:0005343	53.57	gold quality
apex of heart	UBERON:0002098	52.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	49.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	49.04	gold quality
stromal cell of endometrium	CL:0002255	47.74	gold quality
bone marrow cell	CL:0002092	46.38	silver quality
mucosa of transverse colon	UBERON:0004991	46.12	gold quality
duodenum	UBERON:0002114	43.43	gold quality
cerebellum	UBERON:0002037	43.17	gold quality
cerebellar cortex	UBERON:0002129	42.76	gold quality
tonsil	UBERON:0002372	42.26	silver quality
cerebellar hemisphere	UBERON:0002245	42.02	gold quality
ventricular zone	UBERON:0003053	41.66	gold quality
prefrontal cortex	UBERON:0000451	41.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	40.75	gold quality
urinary bladder	UBERON:0001255	40.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	40.38	gold quality
hypothalamus	UBERON:0001898	39.10	gold quality
bone marrow	UBERON:0002371	38.89	silver quality
calcaneal tendon	UBERON:0003701	38.72	silver quality
blood	UBERON:0000178	37.93	gold quality
liver	UBERON:0002107	36.50	gold quality
endocervix	UBERON:0000458	35.71	gold quality
muscle tissue	UBERON:0002385	34.93	gold quality
skeletal muscle tissue	UBERON:0001134	34.89	gold quality
leukocyte	CL:0000738	34.80	gold quality
monocyte	CL:0000576	34.19	gold quality
primary visual cortex	UBERON:0002436	33.34	gold quality
placenta	UBERON:0001987	32.82	gold quality
upper lobe of left lung	UBERON:0008952	32.79	gold quality
cortex of kidney	UBERON:0001225	32.28	gold quality
frontal cortex	UBERON:0001870	32.14	gold quality
lung	UBERON:0002048	32.07	gold quality
kidney	UBERON:0002113	31.86	gold quality
ascending aorta	UBERON:0001496	31.56	gold quality
left uterine tube	UBERON:0001303	31.35	gold quality
thoracic aorta	UBERON:0001515	31.31	gold quality
gall bladder	UBERON:0002110	31.28	gold quality
lymph node	UBERON:0000029	31.10	gold quality
vermiform appendix	UBERON:0001154	31.08	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
ovary	UBERON:0000992	30.87	gold quality
islet of Langerhans	UBERON:0000006	29.80	gold quality
left ovary	UBERON:0002119	29.69	gold quality
right lung	UBERON:0002167	29.51	silver quality
uterine cervix	UBERON:0000002	29.50	gold quality
brain	UBERON:0000955	29.07	gold quality
fallopian tube	UBERON:0003889	28.92	gold quality
tibial artery	UBERON:0007610	28.92	gold quality
popliteal artery	UBERON:0002250	28.83	gold quality
left coronary artery	UBERON:0001626	28.62	gold quality
muscle of leg	UBERON:0001383	27.96	gold quality
omental fat pad	UBERON:0010414	27.71	gold quality
cerebral cortex	UBERON:0000956	27.66	gold quality
adult mammalian kidney	UBERON:0000082	27.62	gold quality
right ovary	UBERON:0002118	27.61	silver quality
multicellular organism	UBERON:0000468	26.96	gold quality
pancreas	UBERON:0001264	26.78	gold quality
putamen	UBERON:0001874	26.54	gold quality
gastrocnemius	UBERON:0001388	25.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	25.61	silver quality
lower esophagus	UBERON:0013473	25.53	silver quality
thoracic mammary gland	UBERON:0005200	25.45	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	25.37	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	25.31	gold quality
heart	UBERON:0000948	25.19	gold quality
right atrium auricular region	UBERON:0006631	25.13	gold quality
adipose tissue	UBERON:0001013	24.98	gold quality
stomach	UBERON:0000945	24.91	silver quality
caudate nucleus	UBERON:0001873	24.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	24.46	gold quality
descending thoracic aorta	UBERON:0002345	24.30	gold quality
endometrium	UBERON:0001295	24.28	gold quality
esophagus	UBERON:0001043	24.25	silver quality
muscle layer of sigmoid colon	UBERON:0035805	24.18	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
adrenal gland	UBERON:0002369	24.06	gold quality
colon	UBERON:0001155	23.89	silver quality
right lobe of liver	UBERON:0001114	23.80	silver quality
intestine	UBERON:0000160	23.68	gold quality
body of stomach	UBERON:0001161	23.62	silver quality
left adrenal gland cortex	UBERON:0035825	23.55	gold quality
skin of abdomen	UBERON:0001416	23.36	gold quality
small intestine	UBERON:0002108	23.36	gold quality
Ammon’s horn	UBERON:0001954	23.18	gold quality
prostate gland	UBERON:0002367	22.98	gold quality
adrenal tissue	UBERON:0018303	22.80	gold quality
zone of skin	UBERON:0000014	22.78	silver quality
thyroid gland	UBERON:0002046	22.70	gold quality
heart left ventricle	UBERON:0002084	22.68	silver quality
nucleus accumbens	UBERON:0001882	22.59	gold quality
tibial nerve	UBERON:0001323	22.28	silver quality
ectocervix	UBERON:0012249	22.28	silver quality
temporal lobe	UBERON:0001871	22.22	gold quality
vagina	UBERON:0000996	22.15	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-HCAD-38	no	1956.73
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

46 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Epididymis	tissue	1489.7
Cerebellum	tissue	30.3
Midbrain	tissue	4.7
Spinal cord	tissue	4.6
Medulla oblongata	tissue	4.2
Corpus callosum	tissue	4.2
Periaqueductal gray	tissue	4.0
Substantia nigra	tissue	3.7
Hippocampal formation	tissue	3.4
Cerebral cortex	tissue	3.3
Hypothalamus	tissue	3.3
Insular cortex	tissue	3.3
Retrosplenial and cingulate cortex	tissue	3.2
Prefrontal cortex	tissue	3.1
Pons	tissue	3.0
Amygdala	tissue	3.0
Ventral forebrain	tissue	3.0
Septum	tissue	3.0
Thalamus	tissue	2.9
Entorhinal cortex	tissue	2.9
Motor cortex	tissue	2.8
Olfactory bulb	tissue	2.8
Somatosensory cortex	tissue	2.8
Basal ganglia	tissue	2.7
Putamen	tissue	2.7
Temporal cortex	tissue	2.7
Superior colliculi	tissue	2.6
Retrosplenial cortex	tissue	2.4
Occipital cortex	tissue	2.4
Locus coeruleus	tissue	0.8
Adrenal gland	tissue	0.7
Seminal vesicle	tissue	0.5
Salivary gland	tissue	0.5
Heart muscle	tissue	0.3
Retina	tissue	0.2
Frontal cortex	tissue	0.2
Gallbladder	tissue	0.2
Thymus	tissue	0.2
Caudate putamen	tissue	0.2
Lymph node	tissue	0.1
Vagina	tissue	0.1
Esophagus	tissue	0.1
Parathyroid gland	tissue	0.1
Urinary bladder	tissue	0.1
Bone marrow	tissue	0.1
Fallopian tube	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 66; highest nTPM — Nucleus tractus solitarii (7.6), Cervical spinal cord, central gray (6.7), Periaquaductal grey, dorsal (6.5), Cervical spinal cord, dorsal horn (5.0), Dorsal spinal cord (4.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KCNIP3, PDX1, POU1F1, POU2F1

Functional genomics

gnomAD constraint: pLI 6.29e-07, LOEUF 1.73, missense Z -0.0908 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000267017 — one region, missense o/e 1.03.

Literature-anchored findings (GeneRIF, showing 7)

• expression of hNPFF2 receptor mRNA was up-regulated by neuropeptide FF (PMID:16336216)
• neuropeptide FF and micro-opioid receptor association could be a possible molecular basis for anti-opioid activity (PMID:17224450)
• the findings from the early studies on the analgesic and morphine modulating activities suggested a role for NPFF in pain modulation–review (PMID:17854890)
• reduction of NPFF release within the dorsal motor nucleus and ambiguus nucleus could serve as a possible cause of the impairment of cardiac vagal control in hypertensive patients (PMID:21120930)
• Our results…highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both migraine with aura and migraine without aura (PMID:26660531)
• The distribution of Neuropeptide FF and Neuropeptide VF in central and peripheral tissues and their role in energy homeostasis control. (PMID:34534716)
• Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure. (PMID:38965251)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npffl	ENSDARG00000045016
mus_musculus	Npff	ENSMUSG00000023052
rattus_norvegicus	Npff	ENSRNOG00000074090

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1891708) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
hyperactivity	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	P15506	100.0%	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
ATF7-AS1	ncRNA	100652999
ATF7	protein-coding	11016
ATF7-NPFF	protein-coding	114108587
ATF7-AS2	ncRNA	124902937
TARBP2	protein-coding	6895
MAP3K12	protein-coding	7786
AMHR2	protein-coding	269
PCBP2	protein-coding	5094
PRR13	protein-coding	54458
PCBP2-OT1	ncRNA	102157401

Protein

Protein identifiers

Pro-FMRFamide-related neuropeptide FF — O15130 (reviewed: O15130)

Alternative names: FMRFamide-related peptides

All UniProt accessions (1): O15130

UniProt curated annotations — full annotation on UniProt →

Function. Morphine modulating peptides. Have wide-ranging physiologic effects, including the modulation of morphine-induced analgesia, elevation of arterial blood pressure, and increased somatostatin secretion from the pancreas. Neuropeptide FF potentiates and sensitizes ASIC1 and ASIC3 channels.

Subcellular location. Secreted.

Similarity. Belongs to the FARP (FMRFamide related peptide) family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15130-1	1	yes
O15130-2	2

RefSeq proteins (2): NP_001307225, NP_003708* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008065	NPFF	Family

Pfam: PF15085

UniProt features (11 total): peptide 3, propeptide 2, modified residue 2, signal peptide 1, sequence variant 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
9JFY	Cryo-EM structure of Neuropeptide FF receptor 2 in complex with hNPSF and Gi	ELECTRON MICROSCOPY	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15130-F1	63.92	0.04

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 9JFY

Human Protein Atlas

Protein class: Predicted secreted proteins

Protein evidence: Evidence at protein level

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 (2)

Type	Positions
Phenylalanine amide	76, 110

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-416476	G alpha (q) signalling events	curated
R-HSA-389397	Orexin and neuropeptides FF and QRFP bind to their respective receptors	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 176 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, MORF_ITGA2, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_REGULATION_OF_BLOOD_PRESSURE, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, GOBP_INSULIN_SECRETION, MORF_BRCA1, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_RESPONSE_TO_FOOD, GOBP_HORMONE_TRANSPORT, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION

GO Biological Process (15): acute inflammatory response to antigenic stimulus (GO:0002438), regulation of membrane depolarization (GO:0003254), positive regulation of cytosolic calcium ion concentration (GO:0007204), neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), response to xenobiotic stimulus (GO:0009410), negative regulation of heart rate (GO:0010459), spinal cord development (GO:0021510), vasopressin secretion (GO:0030103), negative regulation of appetite (GO:0032099), positive regulation of blood pressure (GO:0045777), negative regulation of insulin secretion (GO:0046676), excitatory postsynaptic potential (GO:0060079), maternal process involved in female pregnancy (GO:0060135), somatostatin secretion (GO:0070253)

GO Molecular Function (4): G protein-coupled receptor binding (GO:0001664), signaling receptor binding (GO:0005102), neuropeptide hormone activity (GO:0005184), neuropeptide activity (GO:0160041)

GO Cellular Component (7): extracellular region (GO:0005576), dendrite (GO:0030425), perikaryon (GO:0043204), axon terminus (GO:0043679), postsynapse (GO:0098794), neuronal dense core vesicle (GO:0098992), vesicle (GO:0031982)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

41 GO namespaces:

Category	Terms
cellular anatomical structure	3
peptide hormone secretion	2
inflammatory response to antigenic stimulus	1
acute inflammatory response	1
regulation of membrane potential	1
regulation of cellular process	1
membrane depolarization	1
regulation of biological quality	1
G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
response to chemical	1
regulation of heart rate	1
negative regulation of heart contraction	1
central nervous system development	1
animal gross anatomical part developmental process	1
negative regulation of response to food	1
regulation of appetite	1
regulation of blood pressure	1
insulin secretion	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
female pregnancy	1
multicellular organismal reproductive process	1
signaling receptor binding	1
protein binding	1
hormone activity	1
neuropeptide activity	1
receptor ligand activity	1
neuropeptide receptor binding	1
neuron projection	1
dendritic tree	1
neuronal cell body	1
neuron projection terminus	1
presynapse	1
distal axon	1
synapse	1
dense core granule	1
membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
neuropeptide signaling pathway	BP	direct assay
neuropeptide activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 428 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPFF	NPFFR1	Q9GZQ6	970
NPFF	NPFFR2	Q9Y5X5	965
NPFF	MAS1	P04201	954
NPFF	PRLH	P81277	906
NPFF	PRLHR	P49683	868
NPFF	MRGPRD	Q8TDS7	858
NPFF	MRGPRX2	Q96LB1	852
NPFF	MRGPRX3	Q96LB0	849
NPFF	MRGPRG	Q86SM5	827
NPFF	MRGPRX4	Q96LA9	825
NPFF	MRGPRF	Q96AM1	824
NPFF	MRGPRX1	Q96LB2	820
NPFF	NPVF	Q9HCQ7	813
NPFF	QRFP	P83859	757
NPFF	MAS1L	P35410	725

IntAct

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

1 partners by confidence:

Partner	Interaction type	MIscore	Records
ZDHHC17	physical association	0.370	1

BioGRID (2 interactions; top human partners by supporting records): RNF123 (Affinity Capture-MS), ZDHHC17 (Two-hybrid)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
NPFF	up-regulates	NPFFR1	binding
NPFF	up-regulates	NPFFR2	binding

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
NPFFR2	ligand	Signaling by Neuropeptide precursor
NPFFR1	ligand	Signaling by Neuropeptide precursor

Disease & clinical

Genetic variants

Variant evidence for NPFF: 1 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 115):

Position(s)	Effect	Δscore	Sites
12:53507371–53507372	donor_loss	0.9900	5
12:53507371	donor_loss	0.9800
12:53507019–53507020	donor_loss	0.9500	4
12:53507020	donor_loss	0.9400
12:53507161	acceptor_gain	0.9400
12:53507150	acceptor_gain	0.9200
12:53506894–53506895	acceptor_loss	0.9000	6
12:53507368	donor_loss	0.8700
12:53507143–53507144	acceptor_loss	0.8600	6
12:53507149	acceptor_gain	0.8600

AlphaMissense

99 missense substitutions predicted likely pathogenic (of 723 scored), across 24 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
F110	7	0.941	0.987
F76	7	0.912	0.981
F71	7	0.771	0.864
G111	6	0.865	0.928
K113	6	0.819	0.886
R75	6	0.801	0.900
P73	6	0.770	0.836
F101	5	0.866	0.889
K112	5	0.825	0.906
R109	5	0.780	0.929
W102	5	0.756	0.846
Q108	5	0.748	0.949
P107	5	0.722	0.806
F69	4	0.816	0.880
Q74	4	0.760	0.921
G77	4	0.731	0.828
S103	3	0.717	0.717
R78	3	0.702	0.727
A105	1	0.907	0.907
A106	1	0.729	0.729

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Testicular Germ Cell Tumor)

Disease associations

OMIM: gene MIM:604643 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST005956_63	Waist-to-hip ratio adjusted for BMI	4e-13
GCST005962_45	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7e-13
GCST005958_17	Waist-to-hip ratio adjusted for BMI (age >50)	1e-8
GCST005957_8	Waist-to-hip ratio adjusted for BMI (age <50)	6e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	decreases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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