NALF2

Summary

NALF2 (NALCN channel auxiliary factor 2, HGNC:30701) is a protein-coding gene on chromosome Xq13.1, encoding NALCN channel auxiliary factor 2 (O75949). Probable component of the NALCN channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.

This gene encodes a product belonging to a family of proteins with unknown function. The presence of two transmembrane domains suggests that this protein is a multi-pass membrane protein.

Source: NCBI Gene 27112 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_015686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30701
Approved symbol	NALF2
Name	NALCN channel auxiliary factor 2
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	TED
Ensembl gene	ENSG00000130054
Ensembl biotype	protein_coding
Entrez	27112

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000252338

RefSeq mRNA: 1 — MANE Select: NM_015686 NM_015686

CCDS: CCDS35317

Canonical transcript exons

ENST00000252338 — 3 exons

Exon	Start	End
ENSE00000893212	69528993	69529164
ENSE00001223637	69504326	69506143
ENSE00001296380	69529571	69532508

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 93.28.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2112 / max 46.5583, expressed in 850 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196604	0.5887	324
196606	0.5821	330
196605	0.5786	365
196607	0.4619	277

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	93.28	gold quality
cardiac atrium	UBERON:0002081	90.74	gold quality
right atrium auricular region	UBERON:0006631	90.63	gold quality
apex of heart	UBERON:0002098	88.60	gold quality
left ventricle myocardium	UBERON:0006566	86.95	gold quality
myocardium	UBERON:0002349	85.36	gold quality
diaphragm	UBERON:0001103	84.26	gold quality
heart left ventricle	UBERON:0002084	83.57	gold quality
cardiac ventricle	UBERON:0002082	83.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.37	gold quality
cranial nerve II	UBERON:0000941	80.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.87	gold quality
cervix squamous epithelium	UBERON:0006922	79.76	gold quality
type B pancreatic cell	CL:0000169	79.68	gold quality
heart	UBERON:0000948	79.27	gold quality
vena cava	UBERON:0004087	78.93	gold quality
olfactory bulb	UBERON:0002264	78.09	gold quality
hair follicle	UBERON:0002073	77.02	gold quality
tongue squamous epithelium	UBERON:0006919	75.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.83	gold quality
vastus lateralis	UBERON:0001379	75.41	gold quality
epithelial cell of pancreas	CL:0000083	75.27	gold quality
cortical plate	UBERON:0005343	75.04	gold quality
right lobe of thyroid gland	UBERON:0001119	74.91	gold quality
seminal vesicle	UBERON:0000998	74.85	gold quality
gingival epithelium	UBERON:0001949	74.66	gold quality
cervix epithelium	UBERON:0004801	74.65	gold quality
orbitofrontal cortex	UBERON:0004167	74.57	gold quality
quadriceps femoris	UBERON:0001377	74.38	gold quality
pancreatic ductal cell	CL:0002079	74.24	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

195 targeting NALF2, 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-9-5P	100.00	72.28	2361
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3686	99.90	70.53	2432

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nalf2	ENSDARG00000060152
mus_musculus	Nalf2	ENSMUSG00000071719
rattus_norvegicus	Nalf2	ENSRNOG00000038066
drosophila_melanogaster	Mid1	FBGN0053988

Paralogs (1): NALF1 (ENSG00000204442)

Protein

Protein identifiers

NALCN channel auxiliary factor 2 — O75949 (reviewed: O75949)

Alternative names: Protein TED, Transmembrane protein 28, Transmembrane protein FAM155B

All UniProt accessions (1): O75949

UniProt curated annotations — full annotation on UniProt →

Function. Probable component of the NALCN channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.

Subcellular location. Membrane.

Similarity. Belongs to the NALF family.

RefSeq proteins (1): NP_056501* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR055288	NALCN_aux_factor_1/2	Family

UniProt features (10 total): transmembrane region 2, glycosylation site 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75949-F1	64.07	0.22

Functional residue map

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

Glycosylation sites (2): 120, 193

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, TGACCTY_ERR1_Q2, AP2_Q3, GOBP_MONOATOMIC_CATION_TRANSPORT, COUP_01, MORF_ZNF10, GOBP_CALCIUM_ION_IMPORT, MORF_EPHA7, TTGGAGA_MIR5155P_MIR519E, TCCAGAG_MIR518C, USF_02, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_IMPORT_INTO_CELL, GOBP_TRANSMEMBRANE_TRANSPORT, TGACCTTG_SF1_Q6

GO Biological Process (1): calcium ion import across plasma membrane (GO:0098703)

GO Molecular Function (1): stretch-activated, monoatomic cation-selective, calcium channel activity (GO:0015275)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion import	1
calcium ion transmembrane import into cytosol	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
calcium channel activity	1
mechanosensitive monoatomic cation channel activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NALF2	UNC79	Q9P2D8	577
NALF2	NALCN	Q8IZF0	494
NALF2	UNC80	Q8N2C7	467
NALF2	ZC4H2	Q9NQZ6	466
NALF2	SPIN2B	Q9BPZ2	384
NALF2	MROH7	Q68CQ1	370
NALF2	TMX2	Q9Y320	366
NALF2	HMX2	A2RU54	360
NALF2	LDLRAD1	Q5T700	355
NALF2	DDX49	Q9Y6V7	351
NALF2	OLFML2A	Q68BL7	339
NALF2	HHIPL2	Q6UWX4	324
NALF2	ZNF560	Q96MR9	323
NALF2	C2CD4A	Q8NCU7	322
NALF2	METTL8	Q9H825	322

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2A699, A2ALI5, A2AWH2, A2BDP1, A4IFM1, A4IHZ3, A8MVW0, B0BN44, B1AL88, D3ZZP4, O35144, O35451, O75129, O75949, O94983, P0C7U0, P13265, P51693, P78333, Q03157, Q15554, Q1XFL1, Q2F7Z7, Q3T0Q2, Q3U4N7, Q4W8E7, Q5EGE1, Q5F267, Q5R800, Q5RA50, Q60943, Q61137, Q6H9L7, Q6P9J5, Q6UWH4, Q766D5, Q80Y50, Q80Z10, Q810F0, Q86V42

Diamond homologs: A2AWH2, A2BDP1, A4IFM1, A4IHZ3, B1AL88, O75949, Q8CCS2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

583 predictions. Top by Δscore:

Variant	Effect	Δscore
X:69528989:ACAG:A	acceptor_gain	1.0000
X:69528990:CA:C	acceptor_loss	1.0000
X:69528991:A:AG	acceptor_gain	1.0000
X:69528991:AG:A	acceptor_gain	1.0000
X:69528991:AGGCT:A	acceptor_gain	1.0000
X:69528992:G:GT	acceptor_gain	1.0000
X:69528992:GG:G	acceptor_gain	1.0000
X:69528992:GGC:G	acceptor_gain	1.0000
X:69528992:GGCT:G	acceptor_gain	1.0000
X:69528992:GGCTG:G	acceptor_gain	1.0000
X:69529163:AGG:A	donor_loss	1.0000
X:69529164:GGTA:G	donor_loss	1.0000
X:69529165:G:GC	donor_loss	1.0000
X:69529166:T:A	donor_loss	1.0000
X:69506140:TAAG:T	donor_loss	0.9900
X:69506141:AAGGT:A	donor_loss	0.9900
X:69506142:AGGTA:A	donor_loss	0.9900
X:69506145:T:G	donor_loss	0.9900
X:69528990:C:G	acceptor_gain	0.9900
X:69529125:G:GT	donor_gain	0.9900
X:69529569:AG:A	acceptor_gain	0.9900
X:69529570:GG:G	acceptor_gain	0.9900
X:69506135:GGCT:G	donor_gain	0.9800
X:69506136:GCTG:G	donor_gain	0.9800
X:69528989:A:AG	acceptor_gain	0.9800
X:69528990:CAGG:C	acceptor_gain	0.9800
X:69528991:AGGC:A	acceptor_gain	0.9800
X:69529126:A:T	donor_gain	0.9800
X:69529565:TGGCA:T	acceptor_loss	0.9800
X:69529566:GGCAG:G	acceptor_loss	0.9800

AlphaMissense

3045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:69505878:G:A	C199Y	0.999
X:69529010:G:C	W293C	0.999
X:69529010:G:T	W293C	0.999
X:69529016:C:G	C295W	0.999
X:69529098:T:C	C323R	0.999
X:69505874:T:C	F198L	0.998
X:69505876:T:A	F198L	0.998
X:69505876:T:G	F198L	0.998
X:69505877:T:A	C199S	0.998
X:69505877:T:C	C199R	0.998
X:69505878:G:C	C199S	0.998
X:69505879:C:G	C199W	0.998
X:69506052:C:A	A257D	0.998
X:69529008:T:A	W293R	0.998
X:69529008:T:C	W293R	0.998
X:69529012:T:C	L294P	0.998
X:69529014:T:A	C295S	0.998
X:69529014:T:C	C295R	0.998
X:69529015:G:A	C295Y	0.998
X:69529015:G:C	C295S	0.998
X:69529079:C:G	C316W	0.998
X:69529098:T:A	C323S	0.998
X:69529099:G:C	C323S	0.998
X:69529152:T:C	F341L	0.998
X:69529153:T:G	F341C	0.998
X:69529154:T:A	F341L	0.998
X:69529154:T:G	F341L	0.998
X:69529158:T:A	C343S	0.998
X:69529158:T:C	C343R	0.998
X:69529159:G:A	C343Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000201144 (X:69532820 G>T), RS1000326156 (X:69507350 G>A), RS1000367749 (X:69530540 C>T), RS1000546733 (X:69515680 T>G), RS1000593187 (X:69526010 A>G), RS1000644075 (X:69525626 C>A,T), RS1000843856 (X:69506750 C>T), RS1000886995 (X:69516093 A>C), RS1001023033 (X:69517685 G>A,T), RS1001080190 (X:69518163 C>A), RS1001229711 (X:69504846 C>T), RS1001302524 (X:69507164 G>A,T), RS1001359682 (X:69515209 C>T), RS1001411901 (X:69515705 A>G), RS1001577597 (X:69504506 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007576_51	Chronotype	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
dicrotophos	increases expression	1
bisphenol A	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	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
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cadmium	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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