NARF

Summary

NARF (nuclear prelamin A recognition factor, HGNC:29916) is a protein-coding gene on chromosome 17q25.3, encoding Nuclear prelamin A recognition factor (Q9UHQ1).

Several proteins have been found to be prenylated and methylated at their carboxyl-terminal ends. Prenylation was initially believed to be important only for membrane attachment. However, another role for prenylation appears to be its importance in protein-protein interactions. The only nuclear proteins known to be prenylated in mammalian cells are prelamin A- and B-type lamins. Prelamin A is farnesylated and carboxymethylated on the cysteine residue of a carboxyl-terminal CaaX motif. This post-translationally modified cysteine residue is removed from prelamin A when it is endoproteolytically processed into mature lamin A. The protein encoded by this gene binds to the prenylated prelamin A carboxyl-terminal tail domain. It may be a component of a prelamin A endoprotease complex. The encoded protein is located in the nucleus, where it partially colocalizes with the nuclear lamina. It shares limited sequence similarity with iron-only bacterial hydrogenases. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene, including one with a novel exon that is generated by RNA editing.

Source: NCBI Gene 26502 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_012336

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29916
Approved symbol	NARF
Name	nuclear prelamin A recognition factor
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10067, DKFZp434G0420, IOP2
Ensembl gene	ENSG00000141562
Ensembl biotype	protein_coding
OMIM	605349
Entrez	26502

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 16 protein_coding, 7 retained_intron, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000309794, ENST00000345415, ENST00000374611, ENST00000390006, ENST00000457415, ENST00000577410, ENST00000577432, ENST00000577812, ENST00000578082, ENST00000578820, ENST00000579083, ENST00000579198, ENST00000580296, ENST00000580748, ENST00000581202, ENST00000581743, ENST00000581795, ENST00000582585, ENST00000582907, ENST00000583181, ENST00000583908, ENST00000584192, ENST00000584411, ENST00000584445, ENST00000584513, ENST00000584965, ENST00000852727, ENST00000914809, ENST00000914810, ENST00000914811, ENST00000914812, ENST00000914813

RefSeq mRNA: 4 — MANE Select: NM_012336 NM_001038618, NM_001083608, NM_012336, NM_031968

CCDS: CCDS32777, CCDS42403, CCDS42404

Canonical transcript exons

ENST00000309794 — 11 exons

Exon	Start	End
ENSE00002711155	82487916	82490537
ENSE00002711752	82458741	82458830
ENSE00003458599	82485497	82485654
ENSE00003477275	82481082	82481211
ENSE00003531000	82478800	82478918
ENSE00003574136	82483716	82483779
ENSE00003587154	82472564	82472698
ENSE00003655622	82459992	82460072
ENSE00003664108	82484813	82484950
ENSE00003693176	82464287	82464430
ENSE00003731796	82468764	82468896

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.5954 / max 1324.7588, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163521	23.6661	1803
163520	14.4388	1793
163519	7.4904	1713

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.78	gold quality
right testis	UBERON:0004534	97.74	gold quality
apex of heart	UBERON:0002098	97.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.32	gold quality
cerebellar hemisphere	UBERON:0002245	97.27	gold quality
cerebellar cortex	UBERON:0002129	97.11	gold quality
ganglionic eminence	UBERON:0004023	97.03	gold quality
lower esophagus mucosa	UBERON:0035834	96.88	gold quality
cortical plate	UBERON:0005343	96.77	gold quality
cerebellum	UBERON:0002037	96.50	gold quality
trabecular bone tissue	UBERON:0002483	96.24	gold quality
testis	UBERON:0000473	96.20	gold quality
spleen	UBERON:0002106	96.05	gold quality
granulocyte	CL:0000094	96.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.82	gold quality
blood	UBERON:0000178	95.81	gold quality
ventricular zone	UBERON:0003053	95.64	gold quality
skin of abdomen	UBERON:0001416	95.63	gold quality
right atrium auricular region	UBERON:0006631	95.63	gold quality
right frontal lobe	UBERON:0002810	95.62	gold quality
embryo	UBERON:0000922	95.53	gold quality
skin of leg	UBERON:0001511	95.49	gold quality
adenohypophysis	UBERON:0002196	95.31	gold quality
bone marrow	UBERON:0002371	95.26	gold quality
sperm	CL:0000019	95.23	gold quality
thymus	UBERON:0002370	95.16	gold quality
male germ cell	CL:0000015	95.12	gold quality
caudate nucleus	UBERON:0001873	95.05	gold quality
right lobe of thyroid gland	UBERON:0001119	95.03	gold quality
bone marrow cell	CL:0002092	95.02	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	37.47
E-HCAD-9	yes	6.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting NARF, 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-642A-5P	99.51	65.10	1152
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-874-5P	96.93	63.92	1014

Literature-anchored findings (GeneRIF, showing 6)

• Creation of a novel Alu-exon and elimination of a premature stop codon by RNA editing. (PMID:17326827)
• RNA editing enables exonization of a nuclear prelamin A recognition factor Alu-exon. (PMID:17326827)
• Prelamin A processing is linked to heterochromatin organization. (PMID:17654502)
• Data suggest that gorilla, chimpanzee, and human nuclear prelamin A recognition factor genes exemplify the versatile interplay of pre- and posttranscriptional modifications leading to novel genetic potential. (PMID:18680752)
• Nuclear prelamin a recognition factor and iron dysregulation in multiple sclerosis. (PMID:31823109)
• NARF is a hypoxia-induced coactivator for OCT4-mediated breast cancer stem cell specification. (PMID:36490339)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	narf	ENSDARG00000024184
mus_musculus	Narf	ENSMUSG00000000056
rattus_norvegicus	Narf	ENSRNOG00000036664

Paralogs (2): NDUFS1 (ENSG00000023228), CIAO3 (ENSG00000103245)

Protein

Protein identifiers

Nuclear prelamin A recognition factor — Q9UHQ1 (reviewed: Q9UHQ1)

Alternative names: Iron-only hydrogenase-like protein 2

All UniProt accessions (13): E7EP87, E9PH27, Q9UHQ1, J3KRH7, J3KS03, J3KS48, J3KT43, J3KTG5, J3KTP5, J3QL28, J3QLT6, J3QRB0, J3QSD9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with LMNA and binds to the farnesylated C-terminal domain.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Predominantly expressed in skeletal muscle, heart and brain.

Similarity. Belongs to the NARF family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UHQ1-1	1	yes
Q9UHQ1-2	2
Q9UHQ1-3	3
Q9UHQ1-4	4

RefSeq proteins (4): NP_001033707, NP_001077077, NP_036468, NP_114174 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003149	Fe_hydrogenase_ssu	Domain
IPR004108	Fe_hydrogenase_lsu_C	Domain
IPR009016	Fe_hydrogenase	Homologous_superfamily
IPR050340	Cytosolic_Fe-S_CAF	Family

Pfam: PF02256, PF02906

UniProt features (8 total): splice variant 3, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHQ1-F1	84.03	0.66

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 (1): 29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 137 (showing top): GNF2_ANK1, MODULE_205, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, LEF1_Q6, LIU_VMYB_TARGETS_UP, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GNF2_MAP2K3, GOCC_NUCLEAR_ENVELOPE, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_NUCLEAR_PERIPHERY, GOCC_NUCLEOLUS, GOMF_LAMIN_BINDING, KENNY_CTNNB1_TARGETS_DN

GO Biological Process (0):

GO Molecular Function (1): lamin binding (GO:0005521)

GO Cellular Component (6): lamin filament (GO:0005638), nuclear lamina (GO:0005652), nucleoplasm (GO:0005654), nucleolus (GO:0005730), nuclear lumen (GO:0031981), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nuclear lumen	2
protein binding	1
nuclear lamina	1
intermediate filament	1
nuclear envelope	1
nuclear periphery	1
intracellular membraneless organelle	1
nucleus	1
intracellular organelle lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NARF	EGLN1	Q9GZT9	637
NARF	LMNA	P02545	589
NARF	CIAO1	O76071	471
NARF	CIAPIN1	Q6FI81	452
NARF	GOLM2	Q6P4E1	406
NARF	PCDHB9	Q9Y5E1	401
NARF	ISCU	Q9H1K1	391
NARF	GLRX3	O76003	390
NARF	PLEKHA8	Q96JA3	381
NARF	LYRM4	Q9HD34	379
NARF	NUBP1	P53384	374
NARF	M0R2C6	M0R2C6	369
NARF	MATN3	O15232	368
NARF	SARS2	Q9NP81	368
NARF	ABCB7	O75027	367

IntAct

24 interactions, top by confidence:

A	B	Type	Score
RGS20	GLRX3	psi-mi:“MI:0914”(association)	0.810
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
BOLA2	NARF	psi-mi:“MI:0915”(physical association)	0.400
NARF	SFRP4	psi-mi:“MI:0915”(physical association)	0.370
Nedd1		psi-mi:“MI:0914”(association)	0.350
Ranbp2	POM121C	psi-mi:“MI:0914”(association)	0.350
Ppp4c	NAP1L1	psi-mi:“MI:0914”(association)	0.350
Rab11fip1	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350
PRPF4		psi-mi:“MI:0914”(association)	0.350
Mtmr2	SBF1	psi-mi:“MI:0914”(association)	0.350
Espl1	BDP1	psi-mi:“MI:0914”(association)	0.350
TEPSIN	DERL1	psi-mi:“MI:0914”(association)	0.350
Vangl1		psi-mi:“MI:0914”(association)	0.350
TOR1AIP1	USP1	psi-mi:“MI:0914”(association)	0.350
ACTR5	TBRG1	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
ZNF691	FPGT	psi-mi:“MI:0914”(association)	0.350
RGS20	KIF3B	psi-mi:“MI:0914”(association)	0.350
ISCA2	ARHGEF11	psi-mi:“MI:0914”(association)	0.350
HS1BP3	TAF5L	psi-mi:“MI:0914”(association)	0.350
KCTD17	PXDNL	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350
	NARF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): NARF (Co-localization), NARF (Co-localization), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS), NARF (Affinity Capture-MS)

ESM2 similar proteins: A2RRV9, A4FV58, A4QN59, A7SDA8, A8PGQ3, A8WH18, A8XZU0, B0WU52, B3N018, B3NKH7, B4GXC8, B4IMH3, B4ISL0, B4JBE6, B4KFU7, B4LQR5, B4MUM8, B4NSS7, B5DK31, B6K2N0, O43837, O77784, P29696, P37223, P41565, P51553, P70404, Q16ML2, Q28479, Q2YDU6, Q58CP0, Q5BK18, Q5RBT4, Q5RF36, Q68FX0, Q6CFR3, Q6DE00, Q6DHP6, Q6GP25, Q6ING7

Diamond homologs: A1CIC2, A1CWD8, A2Q9A9, A2RRV9, A3LYR2, A4FV58, A5DKC0, A5DSI2, A6RR15, A6ZRK3, A7E7C4, A7SDA8, A8PGQ3, A8WH18, A8XZU0, B0WU52, B0Y4F9, B3N018, B3NKH7, B4GXC8, B4IMH3, B4ISL0, B4JBE6, B4KFU7, B4LQR5, B4MUM8, B4NSS7, B5DK31, B6HUC4, B6K2N0, B6QQH9, B8N122, B9W8S4, P07598, P0CP10, P0CP11, P13629, P23503, P53998, Q0CR17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3005 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:82478802:T:A	W175R	0.988
17:82478802:T:C	W175R	0.988
17:82484895:G:C	A306P	0.986
17:82472629:T:C	F151L	0.985
17:82472631:C:A	F151L	0.985
17:82472631:C:G	F151L	0.985
17:82484899:C:A	A307D	0.982
17:82485547:T:C	L341S	0.982
17:82485570:T:C	F349L	0.981
17:82485572:T:A	F349L	0.981
17:82485572:T:G	F349L	0.981
17:82484898:G:C	A307P	0.980
17:82472630:T:C	F151S	0.975
17:82485552:T:C	F343L	0.974
17:82485554:T:A	F343L	0.974
17:82485554:T:G	F343L	0.974
17:82478815:C:A	A179D	0.972
17:82481203:T:C	L254S	0.967
17:82485556:C:A	A344D	0.967
17:82478811:T:G	Y178D	0.964
17:82484896:C:A	A306E	0.963
17:82481110:T:A	V223D	0.961
17:82472692:T:C	C172R	0.960
17:82481116:T:A	V225E	0.960
17:82478804:G:C	W175C	0.958
17:82478804:G:T	W175C	0.958
17:82468801:C:T	S97F	0.957
17:82468831:C:A	A107D	0.956
17:82485555:G:C	A344P	0.956
17:82485578:C:A	N351K	0.956

dbSNP variants (sampled 300 via entrez): RS1000215800 (17:82463774 C>T), RS1000270913 (17:82477144 C>T), RS1000342393 (17:82471010 A>G), RS1000375311 (17:82471314 G>A,T), RS1000388936 (17:82490966 T>G), RS1000434637 (17:82460476 T>C,G), RS1000437993 (17:82480666 C>T), RS1000489473 (17:82456355 T>C), RS1000514143 (17:82476659 G>C), RS1000642753 (17:82476984 G>A), RS1000702352 (17:82470273 G>A), RS1000811070 (17:82464827 G>C), RS1000865924 (17:82490810 G>A), RS1000961636 (17:82485558 G>A), RS1000971822 (17:82457544 C>A,T)

Disease associations

OMIM: gene MIM:605349 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
bisphenol A	affects expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Estradiol	affects cotreatment, increases expression	2
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzene	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenomethionine	affects expression	1
Smoke	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1Y6	Abcam HeLa NARF KO	Cancer cell line	Female

Clinical trials (associated diseases)

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