SRP72

Summary

SRP72 (signal recognition particle 72, HGNC:11303) is a protein-coding gene on chromosome 4q12, encoding Signal recognition particle subunit SRP72 (O76094). Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). It is a common-essential gene (DepMap: required in 97.2% of cancer cell lines).

This gene encodes the 72 kDa subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of secretory proteins to the endoplasmic reticulum (ER). The SRP complex consists of a 7S RNA and 6 protein subunits: SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72, that are bound to the 7S RNA as monomers or heterodimers. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein. Mutations in this gene are associated with familial bone marrow failure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6731 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant aplasia and myelodysplasia (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,255 total
• Phenotypes (HPO): 6
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_006947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11303
Approved symbol	SRP72
Name	signal recognition particle 72
Location	4q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174780
Ensembl biotype	protein_coding
OMIM	602122
Entrez	6731

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 5 retained_intron

ENST00000504757, ENST00000505314, ENST00000507126, ENST00000510663, ENST00000642900, ENST00000646222, ENST00000646537, ENST00000646579, ENST00000647432, ENST00000925431, ENST00000925432

RefSeq mRNA: 2 — MANE Select: NM_006947 NM_001267722, NM_006947

CCDS: CCDS3506, CCDS58898

Canonical transcript exons

ENST00000642900 — 19 exons

Exon	Start	End
ENSE00001187275	56500536	56500695
ENSE00001187279	56495357	56495394
ENSE00001187285	56491431	56491568
ENSE00001187291	56490568	56490645
ENSE00001187465	56490333	56490436
ENSE00001187469	56489388	56489483
ENSE00001187473	56487949	56488013
ENSE00001187477	56486325	56486397
ENSE00001187484	56484736	56484864
ENSE00001187490	56483139	56483270
ENSE00001187499	56478592	56478649
ENSE00001187504	56478379	56478503
ENSE00001187512	56476671	56476702
ENSE00001524425	56501684	56503681
ENSE00002051110	56467617	56467744
ENSE00003295998	56474280	56474391
ENSE00003296854	56471720	56471843
ENSE00003369376	56474054	56474197
ENSE00003424722	56469653	56469773

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.2847 / max 1130.1496, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47735	74.2847	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pylorus	UBERON:0001166	98.29	gold quality
tendon of biceps brachii	UBERON:0008188	98.00	gold quality
visceral pleura	UBERON:0002401	97.83	gold quality
parietal pleura	UBERON:0002400	97.75	gold quality
nipple	UBERON:0002030	97.68	gold quality
cardia of stomach	UBERON:0001162	97.65	gold quality
pleura	UBERON:0000977	97.61	gold quality
penis	UBERON:0000989	97.59	gold quality
colonic epithelium	UBERON:0000397	97.56	gold quality
parotid gland	UBERON:0001831	97.49	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.42	gold quality
pericardium	UBERON:0002407	97.42	gold quality
cartilage tissue	UBERON:0002418	97.40	gold quality
bone marrow cell	CL:0002092	97.32	gold quality
tonsil	UBERON:0002372	97.29	gold quality
skin of hip	UBERON:0001554	97.11	gold quality
urethra	UBERON:0000057	97.05	gold quality
substantia nigra pars compacta	UBERON:0001965	97.04	gold quality
corpus epididymis	UBERON:0004359	97.04	gold quality
islet of Langerhans	UBERON:0000006	97.02	gold quality
monocyte	CL:0000576	96.94	gold quality
tendon	UBERON:0000043	96.92	gold quality
mononuclear cell	CL:0000842	96.91	gold quality
calcaneal tendon	UBERON:0003701	96.84	gold quality
type B pancreatic cell	CL:0000169	96.80	gold quality
pharyngeal mucosa	UBERON:0000355	96.77	gold quality
embryo	UBERON:0000922	96.74	gold quality
synovial joint	UBERON:0002217	96.74	gold quality
hair follicle	UBERON:0002073	96.72	gold quality
ganglionic eminence	UBERON:0004023	96.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting SRP72, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• Human SRP RNA bound with high affinity to a 63 amino acid residue region near the C terminus of SRP72 (PMID:15588816)
• Ninety-four amino acids near the C terminus of SRP68 mediated the binding to SRP72 (PMID:16672232)
• Human signal recognition particle RNA with a single A240G change was unable to form a complex with full-length human SRP72. (PMID:18441046)
• Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells. (PMID:20729213)
• The study delineated the minimal region of SRP72 capable of forming a stable complex with an signal recognition particle RNA fragment. (PMID:21073748)
• A heterozygous mutation in SRP72 has a role in familial aplasia and myelodysplasia. (PMID:22541560)
• SRP68/72 heterodimers as major nuclear proteins whose binding of histone H4 tail is inhibited by H4R3 methylation. (PMID:23048028)
• The crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP have been presented. (PMID:27899666)
• The essential role of the SRP68-SRP72 interaction in the signal recognition particle-mediated protein translocation (PMID:28369529)
• SRP72 depletion is associated with elevated levels of apoptosis after irradiation. (PMID:28494188)
• e show that SRP RNA does not bind to the ribosome, while SRP binds with nanomolar affinity involving a two-step mechanism of the key-player SRP54. Ultrasensitive binding of SRP68/72 indicates avidity by multiple binding sites that are dominated by the C-terminus of SRP72 (PMID:30649417)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	srp72	ENSDARG00000014139
mus_musculus	Srp72	ENSMUSG00000036323
rattus_norvegicus	Srp72	ENSRNOG00000002100
rattus_norvegicus	AABR07002546.1	ENSRNOG00000048028
drosophila_melanogaster	Srp72	FBGN0038810
caenorhabditis_elegans		WBGENE00017245

Protein

Protein identifiers

Signal recognition particle subunit SRP72 — O76094 (reviewed: O76094)

Alternative names: Signal recognition particle 72 kDa protein

All UniProt accessions (4): O76094, D6RDY6, R4GNC1, V9HWK0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER. The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER. Binds the signal recognition particle RNA (7SL RNA) in presence of SRP68. Can bind 7SL RNA with low affinity. The SRP complex possibly participates in the elongation arrest function.

Subunit / interactions. Heterodimer with SRP68. SRP68-SRP72 heterodimer formation is stabilized by the presence of 7SL RNA. Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9. Within the SRP complex, interacts (via N-terminus) with SRP68 (via C-terminus).

Subcellular location. Cytoplasm. Endoplasmic reticulum.

Disease relevance. Bone marrow failure syndrome 1 (BMFS1) [MIM:614675] An autosomal dominant disease characterized by aplastic anemia and myelodysplasia resulting from bone marrow failure. Aplastic anemia is a form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. Myelodysplasia is a clonal hematopoietic stem cell disorder in which immature cells in the bone marrow become malformed and dysfunctional. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SRP72 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O76094-1	1	yes
O76094-2	2

RefSeq proteins (2): NP_001254651, NP_008878* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013699	Signal_recog_part_SRP72_RNA-bd	Domain
IPR019734	TPR_rpt	Repeat
IPR026270	SRP72	Family
IPR031545	SRP72_TPR-like	Repeat

Pfam: PF08492, PF13181, PF17004

UniProt features (80 total): helix 28, mutagenesis site 20, modified residue 5, repeat 5, strand 5, region of interest 4, compositionally biased region 4, cross-link 2, turn 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5M72	X-RAY DIFFRACTION	1.6
5WRV	X-RAY DIFFRACTION	1.7
8QVX	ELECTRON MICROSCOPY	2.7
5WRW	X-RAY DIFFRACTION	2.91
8QVW	ELECTRON MICROSCOPY	3
7NFX	ELECTRON MICROSCOPY	3.2
5M73	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76094-F1	82.76	0.67

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 (7): 2, 571, 618, 630, 635, 391, 391

Mutagenesis-validated functional residues (20):

Position	Phenotype
11–44	loss of interaction with srp68.
44	reduced interaction with srp68.
45	reduced interaction with srp68.
53	reduced interaction with srp68. diminished localization to endoplasmic reticulum.
56	loss of interaction with srp72; when associated with a-598 in srp68.
86	loss of interaction with srp68. diminished localization to endoplasmic reticulum.
113–131	loss of interaction with srp68.
132–165	loss of interaction with srp68.
136–137	stronger interaction with srp68.
553–558	loss of rna binding.
555–556	diminished rna binding.
577–578	loss of rna binding.
579–580	diminished rna binding.
579	strongly reduced rna binding.
580	does not affect rna binding.
581–582	diminished rna binding.
583–584	loss of rna binding.
585–586	diminished rna binding.
587–588	no impact on rna binding.
589–590	no impact on rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 167 (showing top): GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, USF_C, PUJANA_CHEK2_PCC_NETWORK, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, WANG_LMO4_TARGETS_DN, MYCMAX_01, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, CYTAGCAAY_UNKNOWN, SCHLOSSER_MYC_TARGETS_AND_SERUM_RESPONSE_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GNF2_DEK, RGAGGAARY_PU1_Q6

GO Biological Process (1): SRP-dependent cotranslational protein targeting to membrane (GO:0006614)

GO Molecular Function (6): RNA binding (GO:0003723), signal recognition particle binding (GO:0005047), 7S RNA binding (GO:0008312), TPR domain binding (GO:0030911), protein binding (GO:0005515), ribosome binding (GO:0043022)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), signal recognition particle, endoplasmic reticulum targeting (GO:0005786), cytosol (GO:0005829), signal recognition particle (GO:0048500), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
ribonucleoprotein complex binding	2
cellular anatomical structure	2
translation	1
cotranslational protein targeting to membrane	1
protein targeting to ER	1
nucleic acid binding	1
RNA binding	1
protein domain specific binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
signal recognition particle	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

1888 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRP72	SRP14	P37108	999
SRP72	SRP9	P49458	999
SRP72	SRP68	Q9UHB9	999
SRP72	SRP19	P09132	999
SRP72	SRP54	P13624	999
SRP72	SRPRA	P08240	833
SRP72	SRPRB	Q9Y5M8	821
SRP72	ANKRD26	Q9UPS8	668
SRP72	CAMK2G	Q13555	588
SRP72	DDX41	Q9UJV9	582
SRP72	SEC61A1	P38378	568
SRP72	SEC63	Q9UGP8	540
SRP72	ETV6	P41212	506
SRP72	MRPL46	Q9H2W6	505
SRP72	GATA2	P23769	475

IntAct

172 interactions, top by confidence:

A	B	Type	Score
SRP9	SRP72	psi-mi:“MI:0914”(association)	0.730
SRP72	SRP68	psi-mi:“MI:0407”(direct interaction)	0.730
SRP72	SRP68	psi-mi:“MI:0915”(physical association)	0.730
SRP68	SRP72	psi-mi:“MI:0914”(association)	0.730
rep	MPHOSPH10	psi-mi:“MI:0914”(association)	0.660
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
SRP14	PPM1G	psi-mi:“MI:0914”(association)	0.640
SULT2B1	SRP72	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
SRP72	SRP19	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SRP68	MAGEB2	psi-mi:“MI:0914”(association)	0.530
	AP3D1	psi-mi:“MI:0914”(association)	0.460
	MYL12B	psi-mi:“MI:0914”(association)	0.460
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
AHI1	OFD1	psi-mi:“MI:2364”(proximity)	0.420
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
SRP72	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
SKIL	SRP72	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (442): SRP72 (Affinity Capture-MS), SRP72 (Affinity Capture-MS), SRP72 (Affinity Capture-MS), SRP72 (Two-hybrid), SRP72 (Affinity Capture-MS), DDX54 (Co-fractionation), GNL3L (Co-fractionation), RRP12 (Co-fractionation), SRP68 (Co-fractionation), SRP72 (Co-fractionation), SRP72 (Co-fractionation), SRP72 (Co-fractionation), SRP72 (Co-fractionation), SRP72 (Co-fractionation), SRP72 (Affinity Capture-MS)

ESM2 similar proteins: A0A644F649, A0AVF1, A1Z8E9, A4III8, A8BS40, A8JA42, A8XBR9, B5X0I6, O17581, O42668, O74458, O76094, O94459, O94474, P11442, P19735, P25870, P29742, P33731, P34574, P41889, P49951, P49965, P53675, P89105, Q00610, Q03560, Q13099, Q16JL4, Q20255, Q29L58, Q4R7Z9, Q57ZL2, Q5CZ52, Q5PR66, Q5U2N8, Q61LA1, Q68FD5, Q6GKV1, Q6INC1

Diamond homologs: O76094, P33731, P49965, P91240

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRP72	“up-regulates activity”	SRP68	binding
SRP19	“up-regulates activity”	SRP72	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 186 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
SRP-dependent cotranslational protein targeting to membrane	22	19.0×	9e-20
Eukaryotic Translation Termination	18	18.6×	3e-16
Peptide chain elongation	17	18.6×	1e-15
Viral mRNA Translation	17	18.6×	1e-15
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	17	18.4×	1e-15
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	18	18.3×	4e-16
Selenocysteine synthesis	17	17.6×	2e-15
Formation of a pool of free 40S subunits	18	17.4×	6e-16

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	18	20.6×	6e-16
ribosomal large subunit biogenesis	6	16.4×	3e-04
ribosomal small subunit biogenesis	9	12.7×	1e-05
translation	19	12.1×	9e-13
rRNA processing	11	9.6×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

1255 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	758
Likely benign	364
Benign	75

Top pathogenic / likely-pathogenic (0)

SpliceAI

2640 predictions. Top by Δscore:

Variant	Effect	Δscore
4:56467740:TAAGA:T	donor_gain	1.0000
4:56467741:AAGA:A	donor_gain	1.0000
4:56467742:AGA:A	donor_gain	1.0000
4:56467742:AGAG:A	donor_loss	1.0000
4:56467743:GA:G	donor_gain	1.0000
4:56467743:GAG:G	donor_gain	1.0000
4:56467743:GAGT:G	donor_loss	1.0000
4:56467744:AGTA:A	donor_loss	1.0000
4:56467745:G:GG	donor_gain	1.0000
4:56467745:GTAA:G	donor_loss	1.0000
4:56469651:A:AG	acceptor_gain	1.0000
4:56469652:G:GA	acceptor_gain	1.0000
4:56469652:GT:G	acceptor_gain	1.0000
4:56469652:GTA:G	acceptor_gain	1.0000
4:56469652:GTAC:G	acceptor_gain	1.0000
4:56469652:GTACT:G	acceptor_gain	1.0000
4:56469730:G:GT	donor_gain	1.0000
4:56469769:GCCAA:G	donor_gain	1.0000
4:56469770:CCAA:C	donor_gain	1.0000
4:56469771:CAA:C	donor_gain	1.0000
4:56469772:AA:A	donor_gain	1.0000
4:56469773:AGT:A	donor_loss	1.0000
4:56469774:G:GG	donor_gain	1.0000
4:56469775:T:A	donor_loss	1.0000
4:56471718:A:AG	acceptor_gain	1.0000
4:56471719:G:GG	acceptor_gain	1.0000
4:56471719:GT:G	acceptor_gain	1.0000
4:56471719:GTA:G	acceptor_gain	1.0000
4:56471719:GTAA:G	acceptor_gain	1.0000
4:56471719:GTAAC:G	acceptor_gain	1.0000

AlphaMissense

4407 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:56469703:T:C	C54R	1.000
4:56469707:T:C	L55P	1.000
4:56471745:T:C	Y86H	1.000
4:56471748:T:C	C87R	1.000
4:56471754:T:C	Y89H	1.000
4:56471758:G:C	R90T	1.000
4:56471758:G:T	R90M	1.000
4:56471761:T:C	L91P	1.000
4:56471778:G:C	A97P	1.000
4:56471830:T:C	L114P	1.000
4:56471836:G:A	G116E	1.000
4:56474061:G:C	R121P	1.000
4:56474083:C:G	C128W	1.000
4:56474140:G:C	R147S	1.000
4:56474140:G:T	R147S	1.000
4:56474149:C:A	N150K	1.000
4:56474149:C:G	N150K	1.000
4:56474151:T:C	L151P	1.000
4:56474377:T:C	L199P	1.000
4:56474385:G:C	A202P	1.000
4:56478615:C:A	A264D	1.000
4:56478631:C:A	N269K	1.000
4:56478631:C:G	N269K	1.000
4:56483151:T:C	F280L	1.000
4:56483153:T:A	F280L	1.000
4:56483153:T:G	F280L	1.000
4:56483155:A:G	D281G	1.000
4:56483157:T:C	S282P	1.000
4:56483162:G:C	K283N	1.000
4:56483162:G:T	K283N	1.000

dbSNP variants (sampled 300 via entrez): RS1000030310 (4:56475862 G>A), RS1000030531 (4:56501159 G>A), RS1000197926 (4:56499787 C>T), RS1000250859 (4:56488896 T>A), RS1000398306 (4:56481890 T>C), RS1000530225 (4:56496769 T>C), RS1000583384 (4:56490444 C>T), RS1000599939 (4:56495578 C>T), RS1000635711 (4:56490845 T>C), RS1000790106 (4:56483499 G>T), RS10007967 (4:56496881 T>A,C), RS1000854958 (4:56488631 A>G), RS1000927264 (4:56482115 A>T), RS1000962203 (4:56477798 G>C), RS1001004270 (4:56495275 A>G)

Disease associations

OMIM: gene MIM:602122 | disease phenotypes: MIM:614675

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant aplasia and myelodysplasia	Strong	Autosomal dominant
acute myeloid leukemia	Moderate	Autosomal dominant

Mondo (2): autosomal dominant aplasia and myelodysplasia (MONDO:0013851), acute myeloid leukemia (MONDO:0018874)

Orphanet (1): Autosomal dominant aplasia and myelodysplasia (Orphanet:314399)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001876	Pancytopenia
HP:0001915	Aplastic anemia
HP:0002863	Myelodysplasia
HP:0005528	Bone marrow hypocellularity

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001621_26	Airflow obstruction	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066168 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.12	Kd	7.631	nM	CHEMBL3752910
8.12	ED50	7.631	nM	CHEMBL3752910
6.21	Kd	613.9	nM	CHEMBL5653589
6.21	ED50	613.9	nM	CHEMBL5653589
5.60	IC50	2500	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 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	2149486: Binding affinity to human SRP72 incubated for 45 mins by Kinobead based pull down assay	kd	0.0076	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149486: Binding affinity to human SRP72 incubated for 45 mins by Kinobead based pull down assay	kd	0.6139	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178669: Inhibition of SRP72 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	2.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	5
Cyclosporine	increases expression, affects cotreatment	4
Air Pollutants	increases abundance, increases oxidation, affects expression, decreases expression, affects cotreatment	3
bisphenol A	affects expression, increases expression	2
nickel sulfate	decreases expression	2
Dinitrochlorobenzene	affects binding, decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
nefazodone	increases expression, affects cotreatment	1
azoxystrobin	increases expression	1
deguelin	increases expression	1
bisphenol B	increases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Atazanavir Sulfate	affects cotreatment, increases expression	1
Oxaliplatin	decreases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652528	Binding	Binding affinity to human SRP72 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)

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

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00000589	PHASE3	COMPLETED	Trial to Reduce Alloimmunization to Platelets (TRAP)
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00093990	PHASE3	COMPLETED	Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00125606	PHASE3	TERMINATED	Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide
NCT00136084	PHASE3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146120	PHASE3	COMPLETED	Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
NCT00150878	PHASE3	TERMINATED	Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
NCT00151255	PHASE3	COMPLETED	All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00152594	PHASE3	TERMINATED	Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
NCT00186966	PHASE3	COMPLETED	Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00226512	PHASE3	WITHDRAWN	To Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00260832	PHASE3	COMPLETED	Trial of Decitabine in Patients With Acute Myeloid Leukemia