SERF1A

Summary

SERF1A (small EDRK-rich factor 1A, HGNC:10755) is a protein-coding gene on chromosome 5q13.2, encoding Small EDRK-rich factor 1 (O75920). Positive regulator of amyloid protein aggregation and proteotoxicity.

This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The duplication region includes both a telomeric and a centromeric copy of this gene. Deletions of this gene, the telomeric copy, often accompany deletions of the neighboring SMN1 gene in spinal muscular atrophy (SMA) patients, and so it is thought that this gene may be a modifier of the SMA phenotype. The function of this protein is not known; however, it bears low-level homology with the RNA-binding domain of matrin-cyclophilin, a protein which colocalizes with small nuclear ribonucleoproteins (snRNPs) and the SMN1 gene product. Alternatively spliced transcripts have been documented but it is unclear whether alternative splicing occurs for both the centromeric and telomeric copies of the gene.

Source: NCBI Gene 8293 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_022968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10755
Approved symbol	SERF1A
Name	small EDRK-rich factor 1A
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	H4F5, 4F5, FAM2A, SMAM1
Ensembl gene	ENSG00000172058
Ensembl biotype	protein_coding
OMIM	603011
Entrez	8293

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000317633, ENST00000354833, ENST00000503509, ENST00000504458, ENST00000507348, ENST00000511162, ENST00000512649, ENST00000512868, ENST00000513436, ENST00000926606

RefSeq mRNA: 2 — MANE Select: NM_022968 NM_021967, NM_022968

CCDS: CCDS47228, CCDS47229

Canonical transcript exons

ENST00000317633 — 3 exons

Exon	Start	End
ENSE00002026180	70907734	70908115
ENSE00002085374	70900669	70900876
ENSE00003460559	70901825	70901933

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.31.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.31	gold quality
right testis	UBERON:0004534	97.98	gold quality
testis	UBERON:0000473	97.39	gold quality
ganglionic eminence	UBERON:0004023	95.30	gold quality
ventricular zone	UBERON:0003053	94.42	gold quality
substantia nigra	UBERON:0002038	94.33	gold quality
hypothalamus	UBERON:0001898	94.10	gold quality
anterior cingulate cortex	UBERON:0009835	94.08	gold quality
amygdala	UBERON:0001876	94.05	gold quality
temporal lobe	UBERON:0001871	93.87	gold quality
caudate nucleus	UBERON:0001873	93.82	gold quality
putamen	UBERON:0001874	93.62	gold quality
mucosa of transverse colon	UBERON:0004991	93.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.19	gold quality
nucleus accumbens	UBERON:0001882	93.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.72	gold quality
right frontal lobe	UBERON:0002810	92.69	gold quality
cortical plate	UBERON:0005343	92.61	gold quality
Ammon’s horn	UBERON:0001954	92.53	gold quality
cerebral cortex	UBERON:0000956	92.49	gold quality
brain	UBERON:0000955	91.97	gold quality
frontal cortex	UBERON:0001870	91.81	gold quality
prefrontal cortex	UBERON:0000451	91.55	gold quality
adenohypophysis	UBERON:0002196	91.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.35	gold quality
transverse colon	UBERON:0001157	91.32	gold quality
descending thoracic aorta	UBERON:0002345	91.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.13	gold quality
rectum	UBERON:0001052	91.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.92
E-MTAB-6524	no	142.22
E-MTAB-7316	no	36.82
E-ANND-3	no	1.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting SERF1A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676

Literature-anchored findings (GeneRIF, showing 6)

• The human orthologs of MOAG-4, SERF2 and SERF1A, are ubiquitously expressed, consistent with a role in a general cellular pathway. (PMID:20723760)
• There is a close relationship between SMN2, NAIP and H4F5 gene copy number and spinal muscular atrophy disease severity (PMID:21821450)
• the autonomous amyloid-modifying activity of SERF1a observed in living organisms relies on a direct and dedicated manipulation of the early stages in the amyloid aggregation pathway. (PMID:22854022)
• Inverse correlation was observed between SMN2, SERF1A and NAIP copy number polymorphism and spinal muscular atrophy type. (PMID:26311540)
• The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation. (PMID:34617299)
• Amyloid Modifier SERF1a Accelerates Alzheimer’s Amyloid-beta Fibrillization and Exacerbates the Cytotoxicity. (PMID:38211979)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serf1	ENSMUSG00000021643
rattus_norvegicus	Serf1	ENSRNOG00000017945

Paralogs (1): SERF1B (ENSG00000205572)

Protein

Protein identifiers

Small EDRK-rich factor 1 — O75920 (reviewed: O75920)

Alternative names: Protein 4F5, SMA modifier 1

All UniProt accessions (7): O75920, D6RC42, D6RC90, D6RCL9, E5RHJ0, E5RIQ9, E5RIX6

UniProt curated annotations — full annotation on UniProt →

Function. Positive regulator of amyloid protein aggregation and proteotoxicity. Induces conformational changes in amyloid proteins, such as APP, HTT, and SNCA, driving them into compact formations preceding the formation of aggregates.

Subunit / interactions. Interacts with SNCA; this interaction promotes the aggregation of SNCA.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Isoform Long is predominantly expressed in heart, brain and skeletal muscle. Isoform Short and Isoform Long are expressed throughout the central nervous system, including spinal cord.

Similarity. Belongs to the SERF family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75920-1	Long	yes
O75920-2	Short

RefSeq proteins (2): NP_068802, NP_075257* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007513	SERF-like_N	Domain
IPR040211	SERF1/2-like	Family

Pfam: PF04419

UniProt features (17 total): mutagenesis site 11, region of interest 2, compositionally biased region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9M27	SOLUTION NMR
9M2D	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75920-F1	63.77	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (11):

Position	Phenotype
13	inhibits snca binding.
14	decreases snca binding.
16	drastically decreases snca binding.
16	inhibits snca binding.
17	drastically decreases snca binding.
17	inhibits snca binding.
18	no effect on snca binding.
11	no effect on snca binding.
11	decreases snca binding.
12	slightly decreases snca binding.
13	decreases snca binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, MODULE_331, GOBP_PROTEIN_DESTABILIZATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_PROTEIN_STABILITY, VANTVEER_BREAST_CANCER_POOR_PROGNOSIS, WALLACE_PROSTATE_CANCER_RACE_DN, BOYLAN_MULTIPLE_MYELOMA_C_D_UP, LEE_RECENT_THYMIC_EMIGRANT, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, VANDESLUIS_COMMD1_TARGETS_GROUP_3_DN, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, GOBP_SUPRAMOLECULAR_FIBER_ORGANIZATION, FORTSCHEGGER_PHF8_TARGETS_UP

GO Biological Process (3): nervous system development (GO:0007399), protein destabilization (GO:0031648), amyloid fibril formation (GO:1990000)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
system development	1
regulation of protein stability	1
protein metabolic process	1
supramolecular fiber organization	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERF1A	NDUFAF3	Q9BU61	919
SERF1A	NAIP	Q13075	872
SERF1A	SMN1	Q16637	839
SERF1A	GPKOW	Q92917	724
SERF1A	C1S	P09871	720
SERF1A	BDP1	A6H8Y1	688
SERF1A	TAAR8	Q969N4	605
SERF1A	GTF2H2	Q13888	599
SERF1A	TPMT	P51580	592
SERF1A	GTF2H2C	Q6P1K8	583
SERF1A	CD82	P27701	582
SERF1A	TAAR6	Q96RI8	517
SERF1A	BACE1	P56817	507
SERF1A	PLS3	P13797	491
SERF1A	ZNF77	Q15935	479

IntAct

44 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
SERF1A	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	CERS4	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	ELOVL7	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	AQP6	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	REEP4	psi-mi:“MI:0915”(physical association)	0.560
ELOVL7	SERF1A	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	TMX2	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	CRB3	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	ABHD16A	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	RNASEK	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	GPR152	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
SERF1A	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SRPK1	SERF1A	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SERF1A	SMC2	psi-mi:“MI:0914”(association)	0.350
PIK3R3	SERF1A	psi-mi:“MI:0915”(physical association)	0.000
SERF1A	TMX2	psi-mi:“MI:0915”(physical association)	0.000
SERF1A	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000
SERF1A	CRB3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): SERF1A (Affinity Capture-MS), SERF1A (Reconstituted Complex), SERF1A (Affinity Capture-RNA), SERF1A (Two-hybrid), SERF1B (Two-hybrid), SERF1A (Two-hybrid), SERF1B (Two-hybrid), SERF1A (Two-hybrid), SERF1B (Two-hybrid), SERF1A (Two-hybrid), SERF1B (Two-hybrid), SERF1A (Two-hybrid), SERF1B (Two-hybrid), SERF1A (Two-hybrid), SERF1B (Two-hybrid)

ESM2 similar proteins: A6NC05, O13533, O13579, O71190, O75920, P0DM64, P0DO27, P12913, P38161, P38808, P38864, P43151, P47126, P53105, P53908, P76163, Q04502, Q08927, Q12169, Q12307, Q13536, Q16612, Q3E751, Q3Y452, Q495C1, Q4R541, Q53S99, Q5NVD3, Q69UP7, Q6B0X1, Q6DN03, Q6Q5F3, Q6Z2K1, Q6ZS49, Q6ZS62, Q6ZS92, Q70YC4, Q8BCV4, Q8FIP8, Q8N0U6

Diamond homologs: A5JSS4, B1MTI8, O75920, O88892, P84101, P84102, Q32P76, Q5R7C4, Q9BKU8, Q9VEW2, Q3E7B7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

609 predictions. Top by Δscore:

Variant	Effect	Δscore
5:70901931:GAG:G	donor_gain	1.0000
5:70901934:G:GC	donor_loss	1.0000
5:70901935:T:G	donor_loss	1.0000
5:70900792:T:TA	donor_gain	0.9900
5:70900793:G:GA	donor_gain	0.9900
5:70900797:ACG:A	donor_gain	0.9900
5:70900852:GC:G	donor_gain	0.9900
5:70900862:T:TA	donor_gain	0.9900
5:70900863:G:GA	donor_gain	0.9900
5:70900877:G:GG	donor_gain	0.9900
5:70901821:GTA:G	acceptor_loss	0.9900
5:70901822:TA:T	acceptor_loss	0.9900
5:70901823:A:AC	acceptor_loss	0.9900
5:70901824:GGT:G	acceptor_gain	0.9900
5:70901934:G:GG	donor_gain	0.9900
5:70907728:TTGTA:T	acceptor_loss	0.9900
5:70907729:TGTA:T	acceptor_loss	0.9900
5:70907731:TAGGG:T	acceptor_loss	0.9900
5:70907732:A:AG	acceptor_gain	0.9900
5:70907732:AG:A	acceptor_gain	0.9900
5:70907733:G:A	acceptor_loss	0.9900
5:70907733:G:GG	acceptor_gain	0.9900
5:70907733:GG:G	acceptor_gain	0.9900
5:70900872:GGCCC:G	donor_gain	0.9800
5:70900873:GCCC:G	donor_gain	0.9800
5:70900873:GCCCG:G	donor_gain	0.9800
5:70901823:A:AG	acceptor_gain	0.9800
5:70901823:AGGT:A	acceptor_gain	0.9800
5:70901824:G:GG	acceptor_gain	0.9800
5:70901824:GGTG:G	acceptor_gain	0.9800

AlphaMissense

416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:70901848:C:A	R11S	0.991
5:70901849:G:C	R11P	0.991
5:70901837:G:C	R7P	0.990
5:70901865:G:C	K16N	0.989
5:70901865:G:T	K16N	0.989
5:70901856:A:C	K13N	0.988
5:70901856:A:T	K13N	0.988
5:70901855:A:T	K13I	0.986
5:70901839:G:A	E8K	0.985
5:70901843:T:C	L9P	0.985
5:70901827:G:A	G4R	0.983
5:70901827:G:C	G4R	0.983
5:70901845:G:C	A10P	0.983
5:70901854:A:G	K13E	0.983
5:70901835:A:C	Q6H	0.982
5:70901835:A:T	Q6H	0.982
5:70901840:A:T	E8V	0.981
5:70901828:G:A	G4E	0.980
5:70901855:A:C	K13T	0.980
5:70901852:A:C	Q12P	0.979
5:70901846:C:A	A10D	0.977
5:70901886:G:C	K23N	0.976
5:70901886:G:T	K23N	0.976
5:70901863:A:G	K16E	0.975
5:70901925:A:C	R36S	0.975
5:70901925:A:T	R36S	0.975
5:70901828:G:T	G4V	0.974
5:70901832:T:A	N5K	0.974
5:70901832:T:G	N5K	0.974
5:70901859:C:A	N14K	0.972

dbSNP variants (sampled 300 via entrez): RS1006299656 (5:70910211 A>G), RS1006314795 (5:70908375 C>A), RS1006332408 (5:70905025 C>T), RS1007836076 (5:70912336 C>T), RS1008217859 (5:70913390 A>AC), RS1015095660 (5:70907471 T>TA), RS1021707130 (5:70912362 C>T), RS1021844082 (5:70913392 A>C), RS1023210734 (5:70913555 T>C), RS1023433189 (5:70912012 T>A,C), RS1030959615 (5:70909017 G>A), RS1031326763 (5:70913471 T>C), RS1036380976 (5:70913152 G>T), RS1036412254 (5:70910234 C>G,T), RS1045084571 (5:70903727 C>T)

Disease associations

OMIM: gene MIM:603011 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	4
Aflatoxin B1	decreases methylation, increases expression	2
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-nonylphenol	affects cotreatment, increases expression	1
CGP 52608	increases reaction, affects binding	1
4-tert-octylphenol	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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