PSD

Summary

PSD (pleckstrin and Sec7 domain containing, HGNC:9507) is a protein-coding gene on chromosome 10q24.32, encoding PH and SEC7 domain-containing protein 1 (A5PKW4). Guanine nucleotide exchange factor for ARF6.

This gene encodes a Plekstrin homology and SEC7 domains-containing protein that functions as a guanine nucleotide exchange factor. The encoded protein regulates signal transduction by activating ADP-ribosylation factor 6. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5662 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 144 total
• GTEx eGene: eQTL in 15 tissues, sQTL in 13 (q < 0.05)
• Constraint (gnomAD): pLI 0.92 (loss-of-function intolerant), LOEUF 0.50 (moderately constrained)
• MANE Select transcript: NM_002779
• Notable: 144 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9507
Approved symbol	PSD
Name	pleckstrin and Sec7 domain containing
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	KIAA2011, TYL, PSD1, EFA6A, EFA6
Ensembl gene	ENSG00000059915
Ensembl biotype	protein_coding
OMIM	602327
Entrez	5662

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000020673

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 1, TSL 5: 1

ENST00000020673, ENST00000406432, ENST00000461698, ENST00000472685, ENST00000473507, ENST00000479172, ENST00000488194, ENST00000492902, ENST00000611678, ENST00000864098, ENST00000864099, ENST00000864100, ENST00000864101, ENST00000864102, ENST00000933096, ENST00000933097, ENST00001141958

RefSeq mRNA: 3 — MANE Select: NM_002779 NM_001270965, NM_001270966, NM_002779

CCDS: CCDS31272, CCDS73187

Canonical transcript exons

ENST00000020673 — 17 exons

Exon	Start	End
ENSE00000722747	102403842	102403985
ENSE00000722749	102404583	102404727
ENSE00000722750	102404898	102405055
ENSE00000722753	102405346	102405536
ENSE00000722760	102411707	102411819
ENSE00000722762	102412381	102412575
ENSE00000811521	102402619	102403430
ENSE00000811524	102413769	102414197
ENSE00001313471	102416385	102417121
ENSE00001317785	102414863	102415229
ENSE00001415244	102418701	102418785
ENSE00002492513	102412147	102412227
ENSE00003273806	102416017	102416119
ENSE00003487570	102405183	102405253
ENSE00003523841	102411058	102411116
ENSE00003537392	102407223	102407266
ENSE00003545336	102410858	102410947

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 99.01.

FANTOM5 (CAGE): breadth broad, TPM avg 10.9893 / max 505.8670, expressed in 734 samples.

Highest expression (Bgee): frontal lobe, cingulate cortex, anterior cingulate cortex, nucleus accumbens, muscle layer of sigmoid colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PSD is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cortex	sqtl	1.6e-57	-1.93	10:102415138:G:A
Brain Frontal Cortex BA9	sqtl	1.1e-55	-1.98	10:102415138:G:A
Brain Anterior cingulate cortex BA24	sqtl	6.6e-34	-1.94	10:102415138:G:A
Brain Caudate basal ganglia	sqtl	1.4e-33	-1.62	10:102415138:G:A
Brain Hippocampus	sqtl	1.1e-24	-1.37	10:102415138:G:A
Brain Nucleus accumbens basal ganglia	sqtl	3.2e-16	-0.97	10:102415138:G:A
Brain Amygdala	sqtl	2.9e-14	-1.43	10:102415138:G:A
Testis	sqtl	5.6e-14	-0.72	10:102404077:G:A
Brain Hypothalamus	sqtl	1.6e-09	-1.23	10:102415138:G:A
Brain Cerebellum	sqtl	1.9e-07	-1.01	10:102415138:G:A
Brain Putamen basal ganglia	sqtl	1.9e-05	-1.43	10:102415138:G:A
Brain Cerebellar Hemisphere	sqtl	3.5e-04	+0.95	10:102132217:C:T
Artery Aorta	eqtl	4.0e-04	+0.70	10:102282852:G:A
Testis	eqtl	4.6e-04	-0.14	10:102219168:T:A
Pituitary	eqtl	3.2e-03	+0.39	10:102265959:C:T
Brain Hypothalamus	eqtl	1.0e-02	+0.60	10:103252457:G:C
Brain Cortex	eqtl	1.2e-02	+0.13	10:102079211:C:T
Heart Atrial Appendage	sqtl	1.2e-02	-1.65	10:101916681:A:C
Skin Sun Exposed Lower leg	eqtl	2.0e-02	+0.67	10:102632875:C:T
Heart Atrial Appendage	eqtl	2.0e-02	-0.17	10:102397954:T:G

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
111157	5.8447	662
111162	2.0714	231
111165	1.6109	153
111164	0.8743	111
111161	0.3396	120
111167	0.1347	71
111158	0.1137	50

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	99.01	gold quality
cingulate cortex	UBERON:0003027	98.52	gold quality
anterior cingulate cortex	UBERON:0009835	98.50	gold quality
nucleus accumbens	UBERON:0001882	98.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.01	gold quality
amygdala	UBERON:0001876	97.88	gold quality
adenohypophysis	UBERON:0002196	97.20	gold quality
caudate nucleus	UBERON:0001873	97.17	gold quality
prefrontal cortex	UBERON:0000451	97.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.67	gold quality
cortical plate	UBERON:0005343	96.63	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.45	gold quality
putamen	UBERON:0001874	96.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.56	gold quality
pituitary gland	UBERON:0000007	95.32	gold quality
cerebellar hemisphere	UBERON:0002245	95.01	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.88	gold quality
frontal cortex	UBERON:0001870	94.87	gold quality
neocortex	UBERON:0001950	94.87	gold quality
frontal lobe	UBERON:0016525	94.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.86	gold quality
cerebellar cortex	UBERON:0002129	94.85	gold quality
frontal pole	UBERON:0002795	94.82	gold quality
lower esophagus	UBERON:0013473	94.77	gold quality
body of uterus	UBERON:0009853	94.18	gold quality
middle frontal gyrus	UBERON:0002702	94.11	gold quality
telencephalon	UBERON:0001893	93.54	gold quality
forebrain	UBERON:0001890	93.28	gold quality
cerebral cortex	UBERON:0000956	93.01	gold quality
Ammon’s horn	UBERON:0001954	92.77	gold quality
left uterine tube	UBERON:0001303	92.72	gold quality
brain	UBERON:0000955	92.30	gold quality
cerebellum	UBERON:0002037	92.14	gold quality
central nervous system	UBERON:0001017	91.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.43	gold quality
endocervix	UBERON:0000458	91.23	gold quality
temporal lobe	UBERON:0001871	91.01	gold quality
sigmoid colon	UBERON:0001159	90.70	gold quality
hypothalamus	UBERON:0001898	90.37	gold quality
smooth muscle tissue	UBERON:0001135	89.69	gold quality
type B pancreatic cell	CL:0000169	88.32	gold quality
CA1 field of hippocampus	UBERON:0003881	88.07	gold quality
ectocervix	UBERON:0012249	87.59	gold quality
islet of Langerhans	UBERON:0000006	87.26	gold quality
right uterine tube	UBERON:0001302	87.21	gold quality
transverse colon	UBERON:0001157	86.43	gold quality
olfactory bulb	UBERON:0002264	86.41	gold quality
superior frontal gyrus	UBERON:0002661	86.31	gold quality
colon	UBERON:0001155	85.84	gold quality
fundus of stomach	UBERON:0001160	85.20	gold quality
ganglionic eminence	UBERON:0004023	85.05	gold quality
primary visual cortex	UBERON:0002436	84.87	gold quality
substantia nigra	UBERON:0002038	84.78	gold quality
large intestine	UBERON:0000059	84.74	gold quality
right ovary	UBERON:0002118	84.58	gold quality
left ovary	UBERON:0002119	84.48	gold quality
occipital lobe	UBERON:0002021	84.03	gold quality
gall bladder	UBERON:0002110	83.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.97	gold quality
midbrain	UBERON:0001891	83.49	gold quality
parietal lobe	UBERON:0001872	83.31	gold quality
parotid gland	UBERON:0001831	83.24	gold quality
body of stomach	UBERON:0001161	83.22	gold quality
postcentral gyrus	UBERON:0002581	83.10	gold quality
left testis	UBERON:0004533	83.10	gold quality
intestine	UBERON:0000160	82.97	gold quality
myometrium	UBERON:0001296	82.78	gold quality
right testis	UBERON:0004534	82.67	gold quality
spinal cord	UBERON:0002240	82.21	gold quality
stomach	UBERON:0000945	82.16	gold quality
entorhinal cortex	UBERON:0002728	81.20	gold quality
sural nerve	UBERON:0015488	81.05	gold quality
esophagus	UBERON:0001043	80.74	gold quality
vagina	UBERON:0000996	80.50	gold quality
inferior olivary complex	UBERON:0002127	80.43	silver quality
testis	UBERON:0000473	80.38	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.10	gold quality
uterine cervix	UBERON:0000002	80.06	gold quality
urinary bladder	UBERON:0001255	79.36	gold quality
ovary	UBERON:0000992	79.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.18	gold quality
paraflocculus	UBERON:0005351	79.07	gold quality
pancreas	UBERON:0001264	78.76	gold quality
uterus	UBERON:0000995	78.58	gold quality
small intestine	UBERON:0002108	78.47	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.38	gold quality
monocyte	CL:0000576	78.08	gold quality
stromal cell of endometrium	CL:0002255	77.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	77.73	gold quality
mononuclear cell	CL:0000842	77.51	gold quality
female reproductive system	UBERON:0000474	77.51	gold quality
leukocyte	CL:0000738	77.10	gold quality
orbitofrontal cortex	UBERON:0004167	77.04	silver quality
fallopian tube	UBERON:0003889	77.03	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	76.76	silver quality
right atrium auricular region	UBERON:0006631	76.71	gold quality
anatomical system	UBERON:0000467	76.35	gold quality
body of pancreas	UBERON:0001150	76.31	gold quality
left adrenal gland cortex	UBERON:0035825	76.20	gold quality
right adrenal gland	UBERON:0001233	76.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.01

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Hippocampus	tissue	487.9
Nucleus accumbens	tissue	348.2
Postcentral gyrus	tissue	259.9
Frontal cortex	tissue	225.0
Caudate putamen	tissue	176.4
Basal ganglia	tissue	169.6
Cerebral cortex	tissue	159.3
Motor cortex	tissue	159.3
Insular cortex	tissue	149.3
Hippocampal formation	tissue	148.7
Prefrontal cortex	tissue	147.0
Somatosensory cortex	tissue	143.6
Putamen	tissue	143.3
Temporal cortex	tissue	143.0
Entorhinal cortex	tissue	140.3
Retrosplenial and cingulate cortex	tissue	132.1
Occipital cortex	tissue	126.5
Retrosplenial cortex	tissue	126.4
Ventral forebrain	tissue	112.6
Amygdala	tissue	106.2
Pituitary gland	tissue	94.8
Locus coeruleus	tissue	90.0
Septum	tissue	77.9
Olfactory bulb	tissue	65.5
Cerebellum	tissue	61.9
Hypothalamus	tissue	35.2
Thalamus	tissue	35.1
Retina	tissue	34.3
Midbrain	tissue	30.1
Superior colliculi	tissue	27.9
Pons	tissue	26.8
Endometrium 1	tissue	22.8
Periaqueductal gray	tissue	18.4
Substantia nigra	tissue	16.9
Smooth muscle	tissue	16.5
Corpus callosum	tissue	15.9
Medulla oblongata	tissue	13.9
Vagina	tissue	13.1
Choroid plexus	tissue	10.6
Urinary bladder	tissue	10.1
Fallopian tube	tissue	9.4
Adrenal gland	tissue	8.6
Gallbladder	tissue	8.3
Spinal cord	tissue	8.1
Colon	tissue	7.4
Duodenum	tissue	5.7
Cervix	tissue	5.5
Ovary	tissue	5.3
Small intestine	tissue	4.8
Testis	tissue	3.7
Pancreas	tissue	3.7
Appendix	tissue	3.6
Stomach 1	tissue	3.5
Rectum	tissue	3.3
Parathyroid gland	tissue	1.4
Epididymis	tissue	1.3
Thymus	tissue	1.3
Skin 1	tissue	1.1
Seminal vesicle	tissue	1.1
Prostate	tissue	1.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Posterior cingulate cortex (515.9), Hippocampus, CA3 (491.4), Hippocampus, CA1 (470.5), Dentate gyrus (469.3), Hippocampus, CA2 (421.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 66 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767

Functional genomics

gnomAD constraint: pLI 0.921, LOEUF 0.504, missense Z 2.68 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000020673 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
10:102,403,203–102,407,229	358 / 426.5	0.84	no
10:102,407,230–102,412,508	110 / 218.7	0.50	no
10:102,412,509–102,417,038	631 / 728.8	0.87	no

Literature-anchored findings (GeneRIF, showing 8)

• Both levels of accumulation of F-actin and apoptosis were significantly decreased in specimens from UC patients with PSD methylation compared to those without PSD methylation. (PMID:22002136)
• Aberrant methylation of PSD occurs in UC-associated colorectal mucosa, enabling circumvention of Rac1 immune responses governing neutrophil chemotaxis and apoptosis, and plays a pivotal role in the mechanisms underlying UC-associated carcinogenesis. (PMID:22179719)
• EFA6 participates in activation of Arf6 around the cleavage furrow during cytokinesis. (PMID:23603394)
• EFA6 is regulated by a negative feedback loop, which is mediated by an allosteric interaction of Arf6-GTP with a domain of EFA6 and monitors the activation of Arf1 and Arf6 differentially (PMID:25114232)
• PSD expression might be a useful biomarker for epigenetic-based gastric cancer early diagnosis and may lead to the identification of new targets for pharmacological intervention. (PMID:25355626)
• Arf GTPases are likely to be locally activated by EFA6 and in turn targeted to the Flemming body to complete cytokinesis. (PMID:26330566)
• EFA6A recruits alpha-actinin 1 (ACTN1) through direct binding. (PMID:29246944)
• The C-terminal domain of EFA6A interacts directly with F-actin and assembles F-actin bundles. (PMID:31844082)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000076702
danio_rerio	psda	ENSDARG00000078102
mus_musculus	Psd	ENSMUSG00000037126
rattus_norvegicus	Psd	ENSRNOG00000019435
drosophila_melanogaster	Efa6	FBGN0051158
caenorhabditis_elegans		WBGENE00013223

Paralogs (15): CYTH3 (ENSG00000008256), MON2 (ENSG00000061987), ARFGEF1 (ENSG00000066777), CYTH4 (ENSG00000100055), CYTH2 (ENSG00000105443), GBF1 (ENSG00000107862), CYTH1 (ENSG00000108669), IQSEC3 (ENSG00000120645), ARFGEF2 (ENSG00000124198), IQSEC2 (ENSG00000124313), PSD4 (ENSG00000125637), IQSEC1 (ENSG00000144711), PSD2 (ENSG00000146005), PSD3 (ENSG00000156011), FBXO8 (ENSG00000164117)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1920978) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal spleen morphology	1
small spleen	1
abnormal eye morphology	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
Chlorocebus aethiops	Q76MZ1	100.0%	Diamond
Bos taurus	O46382	98.3%	Diamond
Arabidopsis thaliana	Q9LPC5	71.4%	Diamond
Dictyostelium discoideum	Q54KA7	54.5%	Diamond
Saccharomyces cerevisiae S288C	P39993	50.6%	Diamond
Schizosaccharomyces pombe 972h-	Q9P7V5	49.5%	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
NFKB2	protein-coding	4791
PITX3	protein-coding	5309
ELOVL3	protein-coding	83401
GBF1	protein-coding	8729
FBXL15	protein-coding	79176
CUEDC2	protein-coding	79004
MIR146B	ncRNA	574447
C10orf95-AS1	ncRNA	100505761
C10orf95	protein-coding	79946
NOLC1	protein-coding	9221

Protein

Protein identifiers

PH and SEC7 domain-containing protein 1 — A5PKW4 (reviewed: A5PKW4)

Alternative names: Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6, Exchange factor for ARF6 A, Pleckstrin homology and SEC7 domain-containing protein 1

All UniProt accessions (2): A0A1B0GUT6, A5PKW4

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor for ARF6. Induces cytoskeletal remodeling.

Subunit / interactions. Interacts with ACTN1. Interacts (ARF6-bound form) with KCNK1; does not interact with KCNK1 in the absence of ARF6.

Subcellular location. Cell membrane. Cell projection. Ruffle membrane. Cleavage furrow.

Tissue specificity. Isoform 2 is expressed in the brain.

Similarity. Belongs to the PSD family.

Isoforms (2)

UniProt ID	Names	Canonical?
A5PKW4-1	1	yes
A5PKW4-2	2

RefSeq proteins (3): NP_001257894, NP_001257895, NP_002770* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000904	Sec7_dom	Domain
IPR001605	PH_dom-spectrin-type	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR023394	Sec7_C_sf	Homologous_superfamily
IPR035999	Sec7_dom_sf	Homologous_superfamily
IPR041681	PH_9	Domain

Pfam: PF01369, PF15410

UniProt features (25 total): compositionally biased region 7, region of interest 5, modified residue 3, sequence conflict 3, domain 2, mutagenesis site 2, chain 1, splice variant 1, coiled-coil region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5PKW4-F1	56.76	0.21

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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 (3)

Type	Positions
Phosphoserine	126, 156, 720

Mutagenesis-validated functional residues (2)

Position	Phenotype
621	loss of gef activity, loss of arf6 localization to the cleavage furrow and, later in cytokinesis, to the midbody ring.
765–766	loss of localization to the plasma membrane during interphase and to the cleavage furrow during cytokinesis. no effect on arf6 localization …

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: 225 (showing top): TGCGCANK_UNKNOWN, TGCACTT_MIR519C_MIR519B_MIR519A, PEREZ_TP63_TARGETS, LFA1_Q6, GCANCTGNY_MYOD_Q6, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, HSIAO_HOUSEKEEPING_GENES, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, MORF_RAD51L3, EFC_Q6, MODULE_66

GO Biological Process (4): signal transduction (GO:0007165), vesicle-mediated transport (GO:0016192), neuron projection development (GO:0031175), regulation of ARF protein signal transduction (GO:0032012)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), phospholipid binding (GO:0005543), protein binding (GO:0005515)

GO Cellular Component (6): cleavage furrow (GO:0032154), ruffle membrane (GO:0032587), dendritic spine (GO:0043197), postsynaptic density, intracellular component (GO:0099092), plasma membrane (GO:0005886), postsynaptic density (GO:0014069)

GO top-level categories

29 GO namespaces:

Category	Terms
cellular process	2
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transport	1
neuron development	1
plasma membrane bounded cell projection organization	1
ARF protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
lipid binding	1
binding	1
cell division site	1
plasma membrane region	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
dendrite	1
neuron spine	1
postsynapse	1
postsynaptic density	1
postsynaptic specialization, intracellular component	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cleavage furrow	CC	direct assay
ruffle membrane	CC	direct assay
guanyl-nucleotide exchange factor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 820 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSD	PISD	Q9UG56	883
PSD	ARF6	P26438	805
PSD	OXA1L	Q15070	791
PSD	CHST15	Q7LFX5	570
PSD	ACAP1	Q15027	559
PSD	ARF1	P10947	558
PSD	RABIF	P47224	474
PSD	ARF5	P26437	452
PSD	M0QZ92	M0QZ92	443
PSD	PLEK2	Q9NYT0	439
PSD	PLEK	P08567	435
PSD	FBXO8	Q9NRD0	430
PSD	GGA3	Q9NZ52	418
PSD	ASAP1	Q9ULH1	413
PSD	ARF4	P18085	376

IntAct

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

9 partners by confidence:

Partner	Interaction type	MIscore	Records
UBC	physical association	0.400	1
ARF6	colocalization	0.270	3
TJP1	colocalization	0.270	1
GLRA2	physical association	0.000	1
GMFG	physical association	0.000	1
GNB5	physical association	0.000	1
HEXD	physical association	0.000	1
HUS1	physical association	0.000	1
RAB40C	physical association	0.000	1

BioGRID (11 interactions; top human partners by supporting records): C16orf72 (Positive Genetic), GNAQ (Affinity Capture-Western), GRASP (Affinity Capture-Western), HEXDC (Two-hybrid), PARP11 (Proximity Label-MS), PARP12 (Proximity Label-MS), PARP2 (Proximity Label-MS), PARP4 (Proximity Label-MS), RAPGEFL1 (Cross-Linking-MS (XL-MS)), TRIM24 (Affinity Capture-MS), VDAC1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for PSD: 144 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	14
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 1,404):

Position(s)	Effect	Δscore	Sites
10:102403840–102403841	donor_loss	1.0000	3
10:102403986–102403987	acceptor_loss	1.0000	3
10:102403991	acceptor_gain	1.0000
10:102403994–102403995	acceptor_gain	1.0000	2
10:102405182	donor_loss	1.0000
10:102405254–102405255	acceptor_loss	1.0000	6
10:102405349	donor_gain	1.0000
10:102412145–102412146	donor_loss	1.0000	5
10:102412412	donor_gain	1.0000
10:102403840–102403841	donor_loss	0.9900	2

AlphaMissense

2,064 missense substitutions predicted likely pathogenic (of 6,560 scored), across 476 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
M673	9	0.991	1.000
M658	9	0.948	1.000
M857	9	0.919	0.991
D663	8	0.998	0.999
F678	8	0.996	1.000
H821	8	0.994	0.997
N661	8	0.993	1.000
F586	8	0.992	1.000
F600	8	0.990	0.999
F571	8	0.987	1.000
F612	8	0.986	0.999
F598	8	0.985	0.999
F632	8	0.985	1.000
N681	8	0.983	0.998
H651	8	0.980	0.998
H665	8	0.979	0.999
D575	8	0.976	0.997
F837	8	0.967	0.999
F691	8	0.965	0.999
F406	8	0.962	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000201
Pancreatic Adenocarcinoma (TCGA)	favorable	0.00084

Disease associations

OMIM: gene MIM:602327 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST010002_100	Refractive error	3e-22
GCST010243_42	Apolipoprotein B levels	2e-10
GCST001942_1	Prostate cancer	5e-10
GCST005962_1	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6e-7
GCST005958_7	Waist-to-hip ratio adjusted for BMI (age >50)	4e-6
GCST005956_7	Waist-to-hip ratio adjusted for BMI	8e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004615	apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523105 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

128 potent at pChembl≥5 of 155 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.60	IC50	250	nM	CHEMBL4574541
6.48	IC50	330	nM	CHEMBL4560033
6.34	IC50	460	nM	CHEMBL4574204
6.30	IC50	500	nM	CHEMBL4525424
6.28	IC50	520	nM	CHEMBL4574204
6.25	IC50	560	nM	CHEMBL4540870
6.24	IC50	580	nM	CHEMBL4585299
6.18	IC50	660	nM	CHEMBL4534219
6.18	IC50	660	nM	CHEMBL4555543
6.17	IC50	670	nM	CHEMBL4540598
6.08	IC50	840	nM	CHEMBL4559227
6.06	IC50	880	nM	CHEMBL4531207
6.02	IC50	960	nM	CHEMBL4546661
6.02	IC50	960	nM	CHEMBL4591591
6.01	IC50	980	nM	CHEMBL4574371
6.00	IC50	1000	nM	CHEMBL4535892
5.96	IC50	1100	nM	CHEMBL4574955
5.96	IC50	1100	nM	CHEMBL4545638
5.96	IC50	1100	nM	CHEMBL4538242
5.96	IC50	1100	nM	CHEMBL4544503
5.96	IC50	1100	nM	CHEMBL4562282
5.96	IC50	1100	nM	CHEMBL4544792
5.96	IC50	1100	nM	CHEMBL4551164
5.96	IC50	1100	nM	CHEMBL4534219
5.96	IC50	1100	nM	CHEMBL593310
5.92	IC50	1200	nM	CHEMBL4538917
5.92	IC50	1200	nM	CHEMBL4522994
5.92	IC50	1200	nM	CHEMBL4571172
5.92	IC50	1200	nM	CHEMBL4522152
5.89	IC50	1300	nM	CHEMBL4570092
5.85	IC50	1400	nM	CHEMBL4537606
5.85	IC50	1400	nM	CHEMBL4584659
5.85	IC50	1400	nM	CHEMBL4553138
5.85	IC50	1400	nM	CHEMBL4570092
5.85	IC50	1400	nM	CHEMBL3716578
5.85	IC50	1400	nM	CHEMBL4584003
5.82	IC50	1500	nM	CHEMBL3716200
5.82	IC50	1500	nM	CHEMBL4579326
5.82	IC50	1500	nM	CHEMBL4553356
5.82	IC50	1500	nM	CHEMBL4528352
5.82	IC50	1500	nM	CHEMBL4564205
5.80	IC50	1600	nM	CHEMBL4538975
5.80	IC50	1600	nM	CHEMBL4571967
5.80	IC50	1600	nM	CHEMBL4559227
5.77	IC50	1700	nM	CHEMBL4591202
5.77	IC50	1700	nM	CHEMBL4538870
5.77	IC50	1700	nM	CHEMBL4527785
5.75	IC50	1800	nM	CHEMBL3716578
5.75	IC50	1800	nM	CHEMBL4578339
5.72	IC50	1900	nM	CHEMBL3716731

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
sodium arsenite	affects methylation	1
ICG 001	decreases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Aspirin	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Lead	affects expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4476963	Binding	Inhibition of N-terminal His-tagged and N-terminal alpha-helix lacking Arf6 (14 to 175 residues) (unknown origin) expressed in Escherichia coli using 20 nM Arf6 in presence of ARNO (50 to 255 residues) incubated for 1 hr by fluorometric hig	Arf6 inhibitors and methods of synthesis and use thereof

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PSD across ~30M SureChEMBL compounds — explore on Sugi Predict.