SSBP1

Summary

SSBP1 (single stranded DNA binding protein 1, HGNC:11317) is a protein-coding gene on chromosome 7q34, encoding Single-stranded DNA-binding protein, mitochondrial (Q04837). Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA). It is a selective cancer dependency (DepMap: 41.3% of cell lines).

SSBP1 is a housekeeping gene involved in mitochondrial biogenesis (Tiranti et al., 1995 [PubMed 7789991]). It is also a subunit of a single-stranded DNA (ssDNA)-binding complex involved in the maintenance of genome stability (Huang et al., 2009) [PubMed 19683501].

Source: NCBI Gene 6742 — RefSeq curated summary.

At a glance

• Gene–disease (curated): optic atrophy 13 with retinal and foveal abnormalities (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 34 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 41.3% of screened cell lines
• MANE Select transcript: NM_003143

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11317
Approved symbol	SSBP1
Name	single stranded DNA binding protein 1
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	SSBP, mtSSB
Ensembl gene	ENSG00000106028
Ensembl biotype	protein_coding
OMIM	600439
Entrez	6742

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 37 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000265304, ENST00000461433, ENST00000463093, ENST00000465167, ENST00000465582, ENST00000467681, ENST00000468267, ENST00000469123, ENST00000473783, ENST00000481508, ENST00000484178, ENST00000489378, ENST00000496622, ENST00000498107, ENST00000612337, ENST00000872103, ENST00000872104, ENST00000872105, ENST00000872106, ENST00000872107, ENST00000872108, ENST00000937880, ENST00000937881, ENST00000937882, ENST00000937883, ENST00000937884, ENST00000937885, ENST00000937886, ENST00000937887, ENST00000937888, ENST00000937889, ENST00000937890, ENST00000937891, ENST00000937892, ENST00000937893, ENST00000937894, ENST00000937895, ENST00000937896, ENST00000937897, ENST00000937898, ENST00000937899, ENST00000937900, ENST00000937901

RefSeq mRNA: 5 — MANE Select: NM_003143 NM_001256510, NM_001256511, NM_001256512, NM_001256513, NM_003143

CCDS: CCDS5866

Canonical transcript exons

ENST00000265304 — 7 exons

Exon	Start	End
ENSE00001206769	141738358	141738410
ENSE00002665815	141750311	141750488
ENSE00003490555	141743561	141743701
ENSE00003583842	141743902	141743989
ENSE00003591454	141745496	141745584
ENSE00003593787	141739124	141739190
ENSE00003787251	141742169	141742229

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 158.5040 / max 2902.9332, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81544	154.1375	1825
81545	3.9225	1576
81547	0.2630	104
81546	0.1811	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.90	gold quality
endometrium	UBERON:0001295	98.61	gold quality
islet of Langerhans	UBERON:0000006	98.52	gold quality
smooth muscle tissue	UBERON:0001135	98.31	gold quality
corpus callosum	UBERON:0002336	98.27	gold quality
rectum	UBERON:0001052	98.16	gold quality
adrenal tissue	UBERON:0018303	98.15	gold quality
monocyte	CL:0000576	98.02	gold quality
leukocyte	CL:0000738	97.98	gold quality
lymph node	UBERON:0000029	97.97	gold quality
endometrium epithelium	UBERON:0004811	97.96	gold quality
vermiform appendix	UBERON:0001154	97.86	gold quality
mucosa of stomach	UBERON:0001199	97.83	gold quality
esophagus mucosa	UBERON:0002469	97.80	gold quality
right adrenal gland	UBERON:0001233	97.79	gold quality
popliteal artery	UBERON:0002250	97.78	gold quality
tibial artery	UBERON:0007610	97.78	gold quality
descending thoracic aorta	UBERON:0002345	97.74	gold quality
uterus	UBERON:0000995	97.71	gold quality
left adrenal gland	UBERON:0001234	97.70	gold quality
placenta	UBERON:0001987	97.69	gold quality
right adrenal gland cortex	UBERON:0035827	97.69	gold quality
esophagus	UBERON:0001043	97.68	gold quality
adrenal gland	UBERON:0002369	97.68	gold quality
ventricular zone	UBERON:0003053	97.68	gold quality
left adrenal gland cortex	UBERON:0035825	97.67	gold quality
heart	UBERON:0000948	97.64	gold quality
left coronary artery	UBERON:0001626	97.64	gold quality
heart left ventricle	UBERON:0002084	97.63	gold quality
ganglionic eminence	UBERON:0004023	97.63	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9689	no	718.67
E-GEOD-124263	no	573.59
E-MTAB-9388	no	10.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZBED1, ZNF331

miRNA regulators (miRDB)

8 targeting SSBP1, 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-6079	99.84	68.54	1170
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-496	98.66	69.80	931
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-890	97.47	68.67	982
HSA-MIR-873-3P	96.84	66.09	786

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 41.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• SSDP1 gene encodes a protein with a conserved N-terminal FORWARD domain;The SSDP1 mRNA transcripts are distributed ubiquitously in adult human and mouse tissues. (PMID:12479417)
• PDIP38 is located in the mitochondrial matrix. TFAM and mitochondrial single-stranded DNA binding protein (mtSSB) are co-immunoprecipitated with PDIP38 (PMID:16428295)
• Zta interaction with mtSSB serves the dual function of facilitating viral and blocking mitochondrial DNA replication. (PMID:18305033)
• Identification of human mitochondrial SSB (HmtSSB) as a novel protein-binding partner of tumour suppressor p53, in mitochondria. (PMID:19066201)
• following DNA damage, SSB1 and Integrator3 relocate to the DNA damage sites and regulate the accumulation of TopBP1 and BRCA1 there (PMID:19759019)
• Data show that mtSSB bound both CKS1 and CKS2 and underwent CDK-dependent phosphorylation. (PMID:19786724)
• Results describe the role of mitochondrial single-stranded DNA binding protein in the maintenance of mitochondrial DNA in cultured human cells. (PMID:20434493)
• hSSB1 may positively modulate p21 to regulate cell cycle progression and DNA damage response, implicating hSSB1 as a novel, promising therapeutic target for cancers such as hepatocellular carcinoma (PMID:21242961)
• mtSSB uses distinct structural elements to interact functionally with its mtDNA replisome partners and to promote proper mtDNA replication in animal cells (PMID:21953457)
• Local enrichment of UNG1 at DNA-bound mtSSB may furthermore facilitate rapid access to- and processing of the damage once the dsDNA conformation is restored. (PMID:22153281)
• Results indicate that hSSB1 may regulate DNA damage checkpoints by positively modulating p53 and its downstream target p21. (PMID:23184057)
• mtSSB potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA. (PMID:23290262)
• In response to the DNA damage response, INTS3-hSSB1-INTS6 complex relocates to the DNA damage sites. (PMID:23986477)
• Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation. (PMID:25249620)
• SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity (PMID:25762445)
• This study determined that hSSB1 acetylation at K94 mediated by the acetyltransferase p300 and the deacetylases SIRT4 and HDAC10 impaired its ubiquitin-mediated degradation by proteasomes. (PMID:26170237)
• The stimulatory effect of mtSSB on Pol gamma on these ssDNA templates is not species-specific. (PMID:26446790)
• The data presented in this study suggests that while SSBP1 has predominantly been considered in a DNA repair context, it is likely to have roles in many other cellular processes. In particular, the identification of numerous proteins with roles in mRNA metabolism, transcriptional transactions and ribosomal processes, may suggest these as important areas of SSBP1 function. (PMID:27938330)
• These results indicated that SSDBP1 may induce cell chemoresistance of cisplatin through promoting DNA repair, resistance-related gene expression, cell proliferation, and inhibiting apoptosis. (PMID:28210897)
• hSSB1 is directly phosphorylated by DNA-PK at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. (PMID:28448822)
• DNA synthesis determines the binding mode of the human mtSSB. (PMID:28486639)
• Data show that single-stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) forms a tetramer and is stabilized by two cysteines (C81 and C99) as well as a subset of charged and hydrophobic residues. (PMID:28609781)
• Data suggest that human mitochondrial SSB shares many physicochemical properties with E coli SSB and that the differences may be explained by the lack of an acidic, disordered C-terminal tail in human mitochondrial SSB protein. (SSB = single-stranded DNA-binding protein) (PMID:28615444)
• Data suggest that human mitochondrial SSB and E coli SSB both protect and expose single-stranded DNA; implications from these studies toward understanding DNA replication and DNA repair abound. (SSB = single-stranded DNA-binding protein) [EDITORIAL] (PMID:28778884)
• This study described a heterozygous start loss mutation in SSBP1 co-segregating with hearing loss in a maternal pedigree transmitting the m.1555A>G variant. (PMID:29182774)
• NEIL1 and homotetrameric mtSSB form a larger ternary complex in presence of DNA, however, the tetrameric form of mtSSB gets disrupted by NEIL1 in the absence of DNA as revealed by the formation of a smaller NEIL1-mtSSBmonomer complex. (PMID:29522991)
• The hSSB1 plays in the maintenance of DNA genomic stability. (PMID:29577982)
• Single-molecule imaging reveals how SSBP1 interacts with single-stranded DNA replication intermediates during mitochondrial DNA synthesis. (PMID:30256971)
• SSBP1 is a novel putative N6-methyldeoxyadenosine (6mA)-binding protein and a mitochondrial DNA (mtDNA) replication factor known to coat the heavy-strand, linking 6mA with the regulation of mtDNA replication. (PMID:30412255)
• This study identified SSBP1 as a putative N6-methyldeoxyadenosine binding protein. (PMID:30412255)
• Proinflammatory IL-6/STAT3 signaling facilitates mtSSB expression. (PMID:30415472)
• These findings suggest that Twinkle is essential for RNA organization in granules, and that mtSSB is involved in the recently proposed GRSF1-mtRNA degradosome pathway, a route suggested to be particularly aimed at degradation of G-quadruplex prone long non-coding mtRNAs. (PMID:30715486)
• findings point toward an essential role of ssbp1 in retinal development. (PMID:31298765)
• mutations in SSBP1 cause a form of dominant optic atrophy frequently accompanied with foveopathy brings insights into mtDNA maintenance disorders. (PMID:31550237)
• SSBP1 mutations associated with an optic atrophy spectrum disorder. (PMID:31550240)
• LncSSBP1 Functions as a Negative Regulator of IL-6 Through Interaction With hnRNPK in Bronchial Epithelial Cells Infected With Talaromyces marneffei. (PMID:31998294)
• Consequences of compromised mitochondrial genome integrity. (PMID:33087282)
• De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans. (PMID:33671400)
• Analysis of Mitochondrial SSB-DNA Complexes and Their Effects on DNA Polymerase gamma Activity by Electron Microscopy and Enzymatic Assays. (PMID:33847964)
• Optical Tweezers to Investigate the Structure and Energetics of Single-Stranded DNA-Binding Protein-DNA Complexes. (PMID:33847965)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ssbp1	ENSDARG00000039350
mus_musculus	Ssbp1	ENSMUSG00000029911
rattus_norvegicus	Ssbp1	ENSRNOG00000012100
drosophila_melanogaster	mtSSB	FBGN0010438
caenorhabditis_elegans		WBGENE00019800

Protein

Protein identifiers

Single-stranded DNA-binding protein, mitochondrial — Q04837 (reviewed: Q04837)

Alternative names: PWP1-interacting protein 17

All UniProt accessions (5): Q04837, A4D1U3, C9J8J0, C9K0U8, E7EUY5

UniProt curated annotations — full annotation on UniProt →

Function. Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA). In vitro, required to maintain the copy number of mitochondrial DNA (mtDNA) and plays a crucial role during mtDNA replication by stimulating the activity of the replisome components POLG and TWNK at the replication fork. Promotes the activity of the gamma complex polymerase POLG, largely by organizing the template DNA and eliminating secondary structures to favor ss-DNA conformations that facilitate POLG activity. In addition it is able to promote the 5’-3’ unwinding activity of the mtDNA helicase TWNK. May also function in mtDNA repair.

Subunit / interactions. Homotetramer. Interacts with MPG/AAG, through inhibition of its glycosylase activity it potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA. Interacts with POLDIP2. Interacts with PRIMPOL.

Subcellular location. Mitochondrion. Mitochondrion matrix. Mitochondrion nucleoid.

Tissue specificity. Expressed in retinal ganglion cells, photoreceptors, pigmented epithelium and fibroblasts (at protein level).

Disease relevance. Optic atrophy 13 with retinal and foveal abnormalities (OPA13) [MIM:165510] An autosomal dominant disease characterized by visual impairment in association with bilateral optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. Many OPA13 patients also exhibit retinal pigmentary defects, attenuated retinal vasculature, macular dystrophy, and foveopathy. Some patients may develop additional systemic features, including sensorineural deafness and progressive nephropathy resulting in renal failure. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (5): NP_001243439, NP_001243440, NP_001243441, NP_001243442, NP_003134* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000424	Primosome_PriB/ssb	Family
IPR011344	ssDNA-bd	Family
IPR012340	NA-bd_OB-fold	Homologous_superfamily

Pfam: PF00436

UniProt features (29 total): strand 9, sequence variant 7, mutagenesis site 5, modified residue 4, transit peptide 1, chain 1, domain 1, helix 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8UZT	X-RAY DIFFRACTION	1.9
6RUP	X-RAY DIFFRACTION	2.1
3ULL	X-RAY DIFFRACTION	2.4
1S3O	X-RAY DIFFRACTION	2.47
2DUD	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04837-F1	83.43	0.63

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 (4): 67, 79, 113, 122

Mutagenesis-validated functional residues (5):

Position	Phenotype
49–51	in mtssbloop12; decreased unwinding of double-stranded dna by the helicase twnk and increased binding to single-stranded
67–75	in mtssbloop23; reduced ability to open template dna and decreased polg polymerase activity, in vitro. also displays dec
99–100	in mtssbalpha1; decreased polg polymerase activity, in vitro. no effect on unwinding of double-stranded dna by the helic
116–118	in mtssb45-1; decreased polg polymerase activity and increased unwinding of double-stranded dna by the helicase twnk, in
122–124	in mtssb45-2; decreased unwinding of double-stranded dna by the helicase twnk, in vitro.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9913635	Strand-asynchronous mitochondrial DNA replication
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-392499	Metabolism of proteins
R-HSA-69306	DNA Replication

MSigDB gene sets: 317 (showing top): MORF_DNMT1, REACTOME_DNA_REPLICATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, MORF_ESPL1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_PROTEIN_HOMOTETRAMERIZATION, BASSO_B_LYMPHOCYTE_NETWORK, MODULE_151, GOBP_MITOCHONDRIAL_DNA_METABOLIC_PROCESS, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN

GO Biological Process (7): DNA replication (GO:0006260), mitochondrial DNA replication (GO:0006264), positive regulation of helicase activity (GO:0051096), protein homotetramerization (GO:0051289), positive regulation of mitochondrial DNA replication (GO:0090297), obsolete mitochondrial genome maintenance (GO:0000002), DNA-templated DNA replication (GO:0006261)

GO Molecular Function (8): chromatin binding (GO:0003682), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), enzyme activator activity (GO:0008047), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial nucleoid (GO:0042645), extracellular exosome (GO:0070062), sperm principal piece (GO:0097228), sperm glycocalyx (GO:0120238)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Mitochondrial biogenesis	1
Metabolism of proteins	1
DNA Replication	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
binding	2
nucleic acid binding	2
intracellular membrane-bounded organelle	2
DNA metabolic process	1
DNA biosynthetic process	1
DNA-templated DNA replication	1
mitochondrial DNA metabolic process	1
helicase activity	1
positive regulation of ATP-dependent activity	1
positive regulation of catalytic activity	1
protein homooligomerization	1
protein tetramerization	1
mitochondrial DNA replication	1
regulation of mitochondrial DNA replication	1
positive regulation of mitochondrial DNA metabolic process	1
positive regulation of DNA-templated DNA replication	1
DNA replication	1
DNA binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
cytoplasm	1
intracellular organelle lumen	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1
extracellular vesicle	1
sperm flagellum	1
cellular anatomical structure	1
glycocalyx	1

Protein interactions and networks

STRING

3696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSBP1	TWNK	Q96RR1	996
SSBP1	TFAM	Q00059	940
SSBP1	POLG	P54098	937
SSBP1	INIP	Q9NRY2	876
SSBP1	SSBP2	P81877	871
SSBP1	POLRMT	O00411	866
SSBP1	INTS3	Q68E01	837
SSBP1	MRPS33	Q9Y291	822
SSBP1	RBBP8	Q99708	786
SSBP1	POLG2	Q9UHN1	756
SSBP1	DNA2	P51530	732
SSBP1	NBN	O60934	723
SSBP1	TFB1M	Q8WVM0	713
SSBP1	TP53	P04637	693
SSBP1	LIG3	P49916	670

IntAct

317 interactions, top by confidence:

A	B	Type	Score
NFYC	NFYA	psi-mi:“MI:0914”(association)	0.850
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
PRELID3B	TRIAP1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
SSBP1	SSBP1	psi-mi:“MI:0407”(direct interaction)	0.670
YY1	YY2	psi-mi:“MI:0914”(association)	0.570
NFIX	NFIB	psi-mi:“MI:0914”(association)	0.570
SSBP1	GCM2	psi-mi:“MI:0915”(physical association)	0.560
LGALS7	SSBP1	psi-mi:“MI:0915”(physical association)	0.560
SSBP1	OTUD6A	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
N	CAVIN2	psi-mi:“MI:0914”(association)	0.530
GATA2	BANF1	psi-mi:“MI:0914”(association)	0.530
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
	BIN1	psi-mi:“MI:0914”(association)	0.460
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
SCLT1	CCDC22	psi-mi:“MI:0914”(association)	0.420
HNF1A	HSPA4L	psi-mi:“MI:0914”(association)	0.420
SSBP1	PAX6	psi-mi:“MI:0914”(association)	0.420
SP1	SSBP1	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (712): SSBP1 (Affinity Capture-MS), INTS3 (Affinity Capture-Western), INTS7 (Affinity Capture-Western), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), TIAL1 (Co-fractionation), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), SSBP1 (Affinity Capture-MS), SSBP1 (Proximity Label-MS)

ESM2 similar proteins: A1L4Y1, A2QCJ2, B8A5I7, F1QR43, F4JP46, P09380, P09381, P27694, P28042, P32445, P35244, P41345, P59931, P59933, P78586, Q01217, Q04837, Q0JJS8, Q28EX9, Q2KJD7, Q32PB0, Q40089, Q4IBU4, Q4X0Z7, Q5AZT7, Q5FW17, Q5FWT7, Q5R4C4, Q5R7Q4, Q5R8R4, Q5RDQ0, Q5ZJJ8, Q641F1, Q69YN2, Q6DI37, Q6NLG7, Q6NWD4, Q6P4T2, Q6STH5, Q7S8C4

Diamond homologs: A6TGW7, B8A5I7, O25841, O69302, P0A2F6, P0A2F7, P0AGE0, P0AGE1, P0AGE2, P0AGE3, P0C118, P18022, P18310, P25762, P28042, P28043, P28044, P28045, P28046, P37455, P40947, P44409, P56898, P57610, P59927, P59928, P59930, P59931, P59932, P59933, P66846, P66847, P66848, P66849, P66854, P77953, Q04837, Q1RK72, Q2YPX7, Q32PB0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 225 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
Mitochondrial protein degradation	10	7.5×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
ubiquinone biosynthetic process	5	23.9×	3e-04
positive regulation of miRNA transcription	8	11.9×	8e-05
cell fate commitment	6	9.1×	5e-03
positive regulation of transcription initiation by RNA polymerase II	6	8.3×	7e-03
transcription by RNA polymerase II	17	6.1×	1e-06
negative regulation of apoptotic process	17	3.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	18
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
977502	NM_003143.3(SSBP1):c.113G>A (p.Arg38Gln)	Pathogenic
977503	NM_003143.3(SSBP1):c.320G>A (p.Arg107Gln)	Pathogenic
977504	NM_003143.3(SSBP1):c.422G>A (p.Ser141Asn)	Pathogenic
977505	NM_003143.3(SSBP1):c.119G>T (p.Gly40Val)	Likely pathogenic

SpliceAI

2069 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141742225:AAGAT:A	donor_gain	1.0000
7:141742226:AGAT:A	donor_gain	1.0000
7:141742227:GAT:G	donor_gain	1.0000
7:141742227:GATG:G	donor_gain	1.0000
7:141742228:AT:A	donor_gain	1.0000
7:141742228:ATGTA:A	donor_loss	1.0000
7:141742229:TGT:T	donor_loss	1.0000
7:141742230:G:C	donor_loss	1.0000
7:141742230:G:GG	donor_gain	1.0000
7:141742231:TAA:T	donor_loss	1.0000
7:141743897:TTTA:T	acceptor_loss	1.0000
7:141743898:TTA:T	acceptor_loss	1.0000
7:141743899:TA:T	acceptor_loss	1.0000
7:141743901:G:GA	acceptor_loss	1.0000
7:141743985:AAGGG:A	donor_gain	1.0000
7:141743986:AGGG:A	donor_gain	1.0000
7:141743987:GGG:G	donor_gain	1.0000
7:141743987:GGGG:G	donor_gain	1.0000
7:141743988:GG:G	donor_gain	1.0000
7:141743988:GGG:G	donor_gain	1.0000
7:141743989:GG:G	donor_gain	1.0000
7:141743989:GGT:G	donor_loss	1.0000
7:141743990:G:GC	donor_loss	1.0000
7:141743990:G:GG	donor_gain	1.0000
7:141743991:T:G	donor_loss	1.0000
7:141745581:GCTG:G	donor_gain	1.0000
7:141738366:G:GT	donor_gain	0.9900
7:141739120:TCAG:T	acceptor_loss	0.9900
7:141739121:CA:C	acceptor_loss	0.9900
7:141739123:G:GC	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000220071 (7:141747551 A>G), RS1000307776 (7:141741841 A>G), RS1000362119 (7:141742056 C>T), RS1000379940 (7:141742452 A>C,G), RS1000572237 (7:141747275 G>A), RS1000874958 (7:141738033 C>T), RS1001267919 (7:141737780 T>C), RS1001443067 (7:141748156 G>A), RS1001541286 (7:141742723 C>T), RS1001554024 (7:141742794 G>C), RS1001694342 (7:141736607 C>A), RS1001771452 (7:141737073 A>C), RS1002096414 (7:141736933 A>T), RS1002523201 (7:141747839 A>G), RS1002545813 (7:141743274 TGC>T)

Disease associations

OMIM: gene MIM:600439 | disease phenotypes: MIM:165510, MIM:120970

GenCC curated gene-disease

Disease	Classification	Inheritance
optic atrophy 13 with retinal and foveal abnormalities	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
optic atrophy 13 with retinal and foveal abnormalities	Strong	AD
Leigh syndrome	Limited	AD

Mondo (5): inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), optic atrophy 13 with retinal and foveal abnormalities (MONDO:0008135), cone-rod dystrophy (MONDO:0015993), retinal disorder (MONDO:0005283)

Orphanet (2): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Cone rod dystrophy (Orphanet:1872)

HPO phenotypes

8 total (9 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000512	Abnormal electroretinogram
HP:0000648	Optic atrophy
HP:0003621	Juvenile onset
HP:0007663	Reduced visual acuity
HP:0007843	Attenuation of retinal blood vessels
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0000556	Retinal dystrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001961_2	Anorexia nervosa	2.000000e-07

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C563494	Optic Atrophy with Negative Electroretinograms (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066314 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.21	Kd	6.21	nM	CHEMBL3752910
8.21	ED50	6.21	nM	CHEMBL3752910
7.46	Kd	34.61	nM	CHEMBL5653589
7.46	ED50	34.61	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149497: Binding affinity to human SSBP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0062	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149497: Binding affinity to human SSBP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0346	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	5
bisphenol A	increases expression, affects cotreatment, decreases expression	4
Acetaminophen	affects cotreatment, affects expression, decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
cobaltous chloride	decreases expression	2
Arsenic	decreases expression, affects cotreatment, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
beauvericin	affects cotreatment, decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases reaction, decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
pinosylvin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
1,4-phenylenebis(methylene)selenocyanate	affects expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
enniatins	affects cotreatment, decreases expression	1
corosolic acid	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	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
CHEMBL5652539	Binding	Binding affinity to human SSBP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)