RBM28

Summary

RBM28 (RNA binding motif protein 28, HGNC:21863) is a protein-coding gene on chromosome 7q32.1, encoding RNA-binding protein 28 (Q9NW13). Nucleolar component of the spliceosomal ribonucleoprotein complexes. It is a selective cancer dependency (DepMap: 85.0% of cell lines).

The protein encoded by this gene is a specific nucleolar component of the spliceosomal small nuclear ribonucleoprotein (snRNP)complexes . It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), possibly coordinating their transition through the nucleolus. Mutation in this gene causes alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome), a pleiotropic and clinically heterogeneous disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55131 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ANE syndrome (Strong, GenCC)
• Clinical variants (ClinVar): 170 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 85.0% of screened cell lines
• MANE Select transcript: NM_018077

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21863
Approved symbol	RBM28
Name	RNA binding motif protein 28
Location	7q32.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10377, NOP4
Ensembl gene	ENSG00000106344
Ensembl biotype	protein_coding
OMIM	612074
Entrez	55131

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000223073, ENST00000415472, ENST00000459726, ENST00000478061, ENST00000481788, ENST00000487602, ENST00000488249, ENST00000495327, ENST00000899022, ENST00000899023, ENST00000899025, ENST00000937193, ENST00000968247, ENST00000968248, ENST00000968249

RefSeq mRNA: 2 — MANE Select: NM_018077 NM_001166135, NM_018077

CCDS: CCDS55159, CCDS5801

Canonical transcript exons

ENST00000223073 — 19 exons

Exon	Start	End
ENSE00000720870	128317659	128317733
ENSE00000720873	128317957	128318106
ENSE00000720875	128321266	128321424
ENSE00000720877	128323527	128323591
ENSE00000720882	128325818	128325891
ENSE00000720884	128330819	128330928
ENSE00000720886	128333290	128333362
ENSE00000720888	128335543	128335679
ENSE00000720890	128335847	128336042
ENSE00000720893	128337131	128337202
ENSE00000720899	128338250	128338342
ENSE00000720903	128338726	128338801
ENSE00000720906	128339227	128339321
ENSE00000720911	128339633	128339791
ENSE00000882258	128343676	128343908
ENSE00000882259	128297685	128310931
ENSE00003507816	128324559	128324694
ENSE00003509317	128314764	128315020
ENSE00003564397	128313175	128313274

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 97.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.9219 / max 617.2054, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86054	32.3774	1810
86053	1.5445	949

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.92	gold quality
calcaneal tendon	UBERON:0003701	94.06	gold quality
apex of heart	UBERON:0002098	93.54	gold quality
right atrium auricular region	UBERON:0006631	91.82	gold quality
gastrocnemius	UBERON:0001388	91.72	gold quality
muscle of leg	UBERON:0001383	91.52	gold quality
colonic epithelium	UBERON:0000397	91.19	gold quality
heart left ventricle	UBERON:0002084	91.04	gold quality
mucosa of stomach	UBERON:0001199	90.82	gold quality
cardiac ventricle	UBERON:0002082	90.62	gold quality
corpus callosum	UBERON:0002336	90.48	gold quality
cardiac atrium	UBERON:0002081	90.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.08	gold quality
tibial nerve	UBERON:0001323	89.61	gold quality
heart	UBERON:0000948	89.56	gold quality
omental fat pad	UBERON:0010414	89.52	gold quality
peritoneum	UBERON:0002358	89.51	gold quality
body of pancreas	UBERON:0001150	89.47	gold quality
left ovary	UBERON:0002119	89.19	gold quality
left testis	UBERON:0004533	89.16	gold quality
tendon	UBERON:0000043	88.94	gold quality
right testis	UBERON:0004534	88.94	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.84	gold quality
body of uterus	UBERON:0009853	88.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.41	gold quality
right adrenal gland cortex	UBERON:0035827	88.21	gold quality
adenohypophysis	UBERON:0002196	88.17	gold quality
muscle organ	UBERON:0001630	88.11	gold quality
right ovary	UBERON:0002118	88.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting RBM28, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-4776-5P	97.14	66.63	405
HSA-MIR-939-5P	97.10	65.80	1579

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 85.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• RBM28 is a common nucleolar component of the spliceosomal ribonucleoprotein complexes, possibly coordinating their transition through the nucleolus (PMID:17081119)
• A loss-of-function mutation is found in RBM28, encoding a nucleolar protein in patients with alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome). (PMID:18439547)
• RBM28 gene defects should be added to the growing list of gene defects associated with syndromic combined anterior pituitary hormone deficiency. (PMID:20231366)
• RBM28 controls the expression of miR-203. RBM28 contributes to hair follicle growth regulation through modulation of miR-203 and p63 activity. (PMID:25939713)
• The authors conclude that the ANE syndrome mutation generates defective RBM28 protein folding which abrogates protein-protein interactions and causes faulty pre-large subunit rRNA processing, thus revealing one aspect of the molecular basis of this human disease. (PMID:27077951)
• Biallelic splicing variants in the nucleolar 60S assembly factor RBM28 cause the ribosomopathy ANE syndrome. (PMID:33941690)
• RNA-binding protein RBM28 can translocate from the nucleolus to the nucleoplasm to inhibit the transcriptional activity of p53. (PMID:34953860)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm28	ENSDARG00000025332
mus_musculus	Rbm28	ENSMUSG00000029701
rattus_norvegicus	Rbm28	ENSRNOG00000005468
drosophila_melanogaster	CG4806	FBGN0260456
caenorhabditis_elegans		WBGENE00017135
caenorhabditis_elegans		WBGENE00017140
caenorhabditis_elegans		WBGENE00020354

Paralogs (6): CELF2 (ENSG00000048740), CELF4 (ENSG00000101489), CELF6 (ENSG00000140488), CELF1 (ENSG00000149187), CELF3 (ENSG00000159409), CELF5 (ENSG00000161082)

Protein

Protein identifiers

RNA-binding protein 28 — Q9NW13 (reviewed: Q9NW13)

Alternative names: RNA-binding motif protein 28

All UniProt accessions (5): Q9NW13, A0A024R753, C9JAA9, C9JE21, H7C5G8

UniProt curated annotations — full annotation on UniProt →

Function. Nucleolar component of the spliceosomal ribonucleoprotein complexes.

Subunit / interactions. Interacts with U1, U2, U4, U5, and U6 spliceosomal small nuclear RNAs (snRNAs).

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Ubiquitously expressed.

Disease relevance. Alopecia, neurologic defects, and endocrinopathy syndrome (ANES) [MIM:612079] Affected individuals have hair loss of variable severity, ranging from complete alopecia to near-normal scalp hair with absence of body hair. All have moderate to severe intellectual disability, progressive motor deterioration and central hypogonadotropic hypogonadism with delayed or absent puberty and central adrenal insufficiency. Additional features included short stature, microcephaly, gynecomastia, pigmentary anomalies, hypodontia, kyphoscoliosis, ulnar deviation of the hands, and loss of subcutaneous fat. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NW13-1	1	yes
Q9NW13-2	2

RefSeq proteins (2): NP_001159607, NP_060547* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR051945	RRM_MRD1_RNA_proc_ribogen	Family

Pfam: PF00076

UniProt features (27 total): compositionally biased region 7, domain 4, sequence conflict 4, modified residue 3, region of interest 3, sequence variant 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NW13-F1	70.39	0.37

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): 2, 122, 397, 653

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 250 (showing top): ONKEN_UVEAL_MELANOMA_UP, chr7q32, GOBP_RNA_SPLICING, DODD_NASOPHARYNGEAL_CARCINOMA_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, REACTOME_METABOLISM_OF_RNA, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_NUCLEOLUS, GOCC_RIBONUCLEOPROTEIN_COMPLEX, LINDGREN_BLADDER_CANCER_CLUSTER_1_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G3_UP, MANALO_HYPOXIA_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, MIKKELSEN_ES_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED

GO Biological Process (2): mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): spliceosomal complex (GO:0005681), nucleolus (GO:0005730), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
mRNA metabolic process	1
nucleic acid binding	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM28	NOP2	P46087	849
RBM28	UTP6	Q9NYH9	576
RBM28	PDCD11	Q14690	559
RBM28	ARHGEF10L	Q9HCE6	537
RBM28	LRRC4	Q9HBW1	535
RBM28	EMG1	Q92979	534
RBM28	BOP1	Q14137	526
RBM28	PAK3	O75914	518
RBM28	SND1	Q7KZF4	505
RBM28	TCFL5	Q9UL49	504
RBM28	TMEM53	Q6P2H8	496
RBM28	WDR12	Q9GZL7	491
RBM28	TBL3	Q12788	484
RBM28	EEF1D	P29692	480
RBM28	NOL12	Q9UGY1	478

IntAct

298 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
RBM28	RSL1D1	psi-mi:“MI:0915”(physical association)	0.560
RBM28	NOP2	psi-mi:“MI:0915”(physical association)	0.560
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
KNOP1	DHX15	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530

BioGRID (472): RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), NOP2 (Co-fractionation)

ESM2 similar proteins: E1BGQ2, P29174, P35922, P55265, P55266, P61798, Q06787, Q12849, Q1RMU2, Q45KJ4, Q45KJ5, Q45KJ6, Q496Y0, Q502M5, Q5EB47, Q5F3F2, Q5R9B4, Q5RED8, Q5VVJ2, Q5XH48, Q5ZLS2, Q66H62, Q69Z66, Q6GLT5, Q6GR37, Q6P5G6, Q6PBM8, Q6ZN17, Q7YRZ2, Q7Z2E3, Q803L0, Q80TQ2, Q80WE1, Q8AVK2, Q8C5Q4, Q8IWR0, Q8JHC4, Q8K3Y3, Q8NHU6, Q99MU3

Diamond homologs: A0A0D1C8Z4, A1A5R1, A2A5N3, A3LXL0, A4F5G6, A5A6M3, A5DW14, A6NFN3, A6QPR6, F1QB54, F4HT49, O04319, O13845, O35698, O43251, O93235, P0CB38, P11940, P19682, P19683, P19684, P20965, P28644, P29341, P38159, P42731, P49313, P49314, P60824, P60825, P60826, P61286, P62995, P62996, P62997, Q04836, Q08935, Q08937, Q09511, Q0VD23

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 237 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
Peptide chain elongation	16	13.0×	8e-12
Viral mRNA Translation	16	13.0×	8e-12
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	16	12.9×	8e-12
Selenocysteine synthesis	16	12.3×	1e-11
Eukaryotic Translation Termination	16	12.3×	1e-11
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	16	12.1×	1e-11
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	16	12.1×	1e-11
SRP-dependent cotranslational protein targeting to membrane	18	11.6×	3e-12

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	18	15.5×	1e-13
ribosomal large subunit biogenesis	7	14.4×	1e-04
peptidyl-tyrosine phosphorylation	7	13.7×	2e-04
positive regulation of viral genome replication	5	13.5×	3e-03
negative regulation of viral genome replication	7	12.2×	3e-04
mitotic spindle assembly	7	11.2×	4e-04
regulation of signal transduction by p53 class mediator	6	10.7×	2e-03
ribosomal small subunit biogenesis	10	10.6×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	103
Likely benign	27
Benign	8

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
732	NM_018077.3(RBM28):c.1052T>C (p.Leu351Pro)	Pathogenic
802364	NM_018077.3(RBM28):c.541+1del	Pathogenic
2691762	NM_018077.3(RBM28):c.1489_1492dup (p.Val498fs)	Likely pathogenic
802363	NM_018077.3(RBM28):c.946G>T (p.Ala316Ser)	Likely pathogenic

SpliceAI

2681 predictions. Top by Δscore:

Variant	Effect	Δscore
7:128313170:CTCA:C	donor_loss	1.0000
7:128313172:CA:C	donor_loss	1.0000
7:128313173:A:AC	donor_gain	1.0000
7:128313173:A:AG	donor_loss	1.0000
7:128313174:C:A	donor_loss	1.0000
7:128313174:C:CC	donor_gain	1.0000
7:128313174:CCTG:C	donor_gain	1.0000
7:128313271:CAAC:C	acceptor_gain	1.0000
7:128313275:C:CA	acceptor_loss	1.0000
7:128313276:T:G	acceptor_loss	1.0000
7:128315016:TTTTG:T	acceptor_gain	1.0000
7:128315017:TTTG:T	acceptor_gain	1.0000
7:128315018:TTG:T	acceptor_gain	1.0000
7:128315018:TTGC:T	acceptor_loss	1.0000
7:128315019:TG:T	acceptor_gain	1.0000
7:128315020:GCT:G	acceptor_loss	1.0000
7:128315021:C:CC	acceptor_gain	1.0000
7:128315024:C:CT	acceptor_gain	1.0000
7:128315025:A:C	acceptor_gain	1.0000
7:128317623:ATGT:A	donor_gain	1.0000
7:128317626:T:TA	donor_gain	1.0000
7:128317658:CCAAG:C	donor_gain	1.0000
7:128317662:G:C	donor_gain	1.0000
7:128317952:CCTA:C	donor_loss	1.0000
7:128317953:CTAC:C	donor_loss	1.0000
7:128317954:TACCT:T	donor_loss	1.0000
7:128317955:ACC:A	donor_loss	1.0000
7:128317956:C:A	donor_loss	1.0000
7:128318102:CTACA:C	acceptor_gain	1.0000
7:128318103:TACA:T	acceptor_gain	1.0000

AlphaMissense

5032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:128318038:A:C	F544L	0.999
7:128318038:A:T	F544L	0.999
7:128318040:A:G	F544L	0.999
7:128321378:A:T	V484D	0.999
7:128325881:A:C	F380L	0.999
7:128325881:A:T	F380L	0.999
7:128325883:A:G	F380L	0.999
7:128333295:A:C	F338L	0.999
7:128333295:A:T	F338L	0.999
7:128333297:A:G	F338L	0.999
7:128338315:A:T	V159D	0.999
7:128338317:A:C	F158L	0.999
7:128338317:A:T	F158L	0.999
7:128338319:A:G	F158L	0.999
7:128339230:A:C	F123L	0.999
7:128339230:A:T	F123L	0.999
7:128339232:A:G	F123L	0.999
7:128339761:A:T	V50D	0.999
7:128317716:G:C	F577L	0.998
7:128317716:G:T	F577L	0.998
7:128317718:A:G	F577L	0.998
7:128321399:A:G	L477P	0.998
7:128323533:T:A	R466S	0.998
7:128323533:T:G	R466S	0.998
7:128333299:A:T	V337D	0.998
7:128338323:A:C	F156L	0.998
7:128338323:A:T	F156L	0.998
7:128338325:A:G	F156L	0.998
7:128317717:A:G	F577S	0.997
7:128325879:G:T	A381D	0.997

dbSNP variants (sampled 300 via entrez): RS1000002551 (7:128334758 C>G), RS1000146744 (7:128328788 T>C), RS1000155415 (7:128322789 C>G,T), RS1000412801 (7:128310348 CA>C,CAA), RS1000461037 (7:128324319 T>C), RS1000519881 (7:128328983 T>C), RS1000809181 (7:128299460 T>C), RS1000892085 (7:128311971 C>T), RS1000906583 (7:128329842 T>C), RS1001008099 (7:128336334 A>G), RS1001042215 (7:128336027 T>C), RS1001083676 (7:128298876 G>C,T), RS1001100392 (7:128342069 G>T), RS1001166081 (7:128313586 G>A), RS1001290760 (7:128342762 G>C)

Disease associations

OMIM: gene MIM:612074 | disease phenotypes: MIM:612079

GenCC curated gene-disease

Disease	Classification	Inheritance
ANE syndrome	Strong	Autosomal recessive

Mondo (2): ANE syndrome (MONDO:0012794), microcephaly (MONDO:0001149)

Orphanet (1): ANE syndrome (Orphanet:157954)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000252	Microcephaly
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000771	Gynecomastia
HP:0000823	Delayed puberty
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000953	Hyperpigmentation of the skin
HP:0000995	Melanocytic nevus
HP:0001249	Intellectual disability
HP:0001596	Alopecia
HP:0002333	Motor deterioration
HP:0002493	Upper motor neuron dysfunction
HP:0002750	Delayed skeletal maturation
HP:0002751	Kyphoscoliosis
HP:0002828	Multiple joint contractures
HP:0003121	Limb joint contracture
HP:0003202	Skeletal muscle atrophy
HP:0003700	Generalized amyotrophy
HP:0003758	Reduced subcutaneous adipose tissue
HP:0004322	Short stature
HP:0006480	Premature loss of teeth
HP:0007373	Motor neuron atrophy
HP:0007481	Hyperpigmented nevi
HP:0008202	Reduced circulating prolactin concentration
HP:0008245	Pituitary hypothyroidism
HP:0009487	Ulnar deviation of the hand
HP:0010627	Anterior pituitary hypoplasia
HP:0011734	Central adrenal insufficiency

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C567425	Alopecia, Neurologic Defects, and Endocrinopathy Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067374 (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
7.68	Kd	21.04	nM	CHEMBL3752910
7.68	ED50	21.04	nM	CHEMBL3752910
5.76	Kd	1751	nM	CHEMBL5653589
5.76	ED50	1751	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	2149207: Binding affinity to human RBM28 incubated for 45 mins by Kinobead based pull down assay	kd	0.0210	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149207: Binding affinity to human RBM28 incubated for 45 mins by Kinobead based pull down assay	kd	1.7512	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis, affects methylation	2
Nickel	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, increases methylation	2
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
sodium arsenite	decreases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	increases expression	1
beta-Naphthoflavone	affects cotreatment, decreases expression	1
Copper Sulfate	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
CHEMBL5652249	Binding	Binding affinity to human RBM28 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)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.